Positive Antinuclear Antibody Research Articles

Genetic Analysis of Asymptomatic Antinuclear Antibody Production.

Antinuclear antibodies (ANA) are detected in up to 14% of the population, and many individuals with ANA are asymptomatic. The literature on the genetic contribution to asymptomatic ANA positivity is limited. In this study, we aimed to perform a genome-wide association study of asymptomatic ANA positivity in multiple populations. Asymptomatic individuals who were either ANA positive or ANA negative from the All of Us Research Program were included in this study, selecting those with an ANA test performed by immunofluorescence and no evidence of autoimmune disease. Imputation was performed, and a multipopulation meta-analysis including approximately 6 million single-nucleotide polymorphisms (SNPs) was conducted. Genome-wide SNP-based heritability was estimated using the Genome-wide Complex Trait Analysissoftware. A cumulative genetic risk score for lupus was constructed using previously reported genome-wide significant loci. A total of 1,955 asymptomatic ANA positive and 3,634 asymptomatic ANA negative individuals across three populations were included. The multipopulation meta-analysis revealed SNPs with a suggestive association (P <1 × 10-5) across 8 different loci, but no genome-wide significant loci were identified. A gene variant upstream of HLA-DQB1, (rs17211748, P = 1.4 × 10-6, odds ratio 0.82, 95% confidence interval 0.76-0.89), showed the most significant association. The heritability of asymptomatic ANA positivity was estimated to be 24.9%. Individuals who were asymptomatic and ANA positive did not exhibit increased cumulative genetic risk for lupus compared with individuals who were ANA negative. ANA production is not associated with significant genetic risk and is primarily determined by environmental factors.

Analysis of antinuclear antibody in 9 528 pregnant women during early pregnancy in a hospital in Qingdao City

To analyze the positivity rate and titer of antinuclear antibody (ANA), as well as nuclear pattern and target antigen of ANA in healthy pregnant women during early pregnancy in Qingdao area. A prospective cohort study design was used to include a total of 9 528 healthy pregnant women registered at the Women and Children's Hospital Affiliated to Qingdao University from March 2023 to June 2024.Indirect immunofluorescence assay (IIF) was used to detect ANA, its titer and cell staining pattern. Fifteen specific antibodies were tested using the magnetic bar code immunofluorescent luminescence method. Logistic regression model was used to analyze the risk factors of pregnancy with autoimmune disease(AID). The results showed that among 9 528 pregnant women in early pregnancy, 1 346 cases (14.1%) were positive of ANA, including 1 011 cases with a titer of 1∶100 (10.6%), 236 cases (2.5%) with a titer of 1∶320, and 99 cases (1.0%) were detected at a titer >1∶320. Among the 1 346 ANA-positive pregnant women, nuclear granular type accounted for the highest proportion (483 cases, 35.9%), followed by speckled type (347 cases, 25.8%) and cytoplasmic type (176 cases, 13.1%).Then, pregnant women with ANA titers ≥1∶100 were detected 15 specific antibodies.Anti-SSA was tested in 121 cases accounted for the majority, followed by 110 cases with anti-Ro-52, 56 cases with anti-SSB, 51 cases with anti-mitochondrial M2 subtype antibodies and 37 cases with anti-centromere B. In conclusion,in healthy pregnant women in Qingdao area, ANA positivity rate was 14.1%, and the titer of ANA was mainly at 1∶100.The predominant nuclear patterns were nuclear granular and speckled types.The specific autoantibodies were mainly anti-SSA antibodies and anti-Ro-52 antibodies.The detection of ANA and specific autoantibodies is of great significance for early prediction, diagnosis, and intervention of autoimmune diseases during pregnancy.

Recurrent catatonia in a patient with bipolar disorder and polycythemia: A case report

We report the diagnostic and management challenges encountered in a case of a 57-year-old male patient with bipolar I disorder and comorbid polycythemia secondary to obstructive sleep apnea, who was treated in our inpatient psychiatric unit for suicidal ideation and recurrent catatonia. He was found to have catatonia with a Bush&amp;ndash;Francis Catatonia Rating Scale score of 18. He subsequently exhibited a positive response to the lorazepam challenge test. Before discharge, his daily lorazepam dose was titrated to 6 mg, which led to resolution of catatonic symptoms, and was tapered to discontinuation. During the second hospitalization, the patient&amp;rsquo;s catatonia returned, but due to lorazepam-induced bradycardia, he refrained from taking more than 1 mg of the medication. Divalproex sodium and memantine were initiated as off-label catatonic treatment plus lurasidone for bipolar depression. The patient was also found to have a positive antinuclear antibody titer (1:160). The hemato-immunological abnormalities present in our patient complicated his catatonic condition, underscoring the need to explore medical and neuropsychiatric catatonic factors for accurate diagnosis of this neuropsychiatric syndrome.

P49 Belimumab as a potential therapy for lupus enteritis – a case report

Abstract Introduction Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with varied clinical manifestations. Gastrointestinal (GI) complaints are common in 40–60% of SLE patients. Most are mild; however severe life-threatening manifestations may occur. Lupus enteritis (LE) is a rare but severe GI manifestation of SLE, characterised by vasculitis or inflammation of the bowel. Belimumab is a recombinant human monoclonal antibody against the soluble B-lymphocyte stimulator protein (BLyS) and was the first licensed treatment for SLE and lupus nephritis. Herein, we report a case of lupus enteritis that responded well to belimumab therapy. Case description We present a 42-year-old Sri Lankan woman who was diagnosed with SLE in 2015 based on arthritis, Raynaud’s, haemoproteinuria, positive antinuclear antibodies (ANA), anti-double stranded DNA (dsDNA), and anti-Ro antibodies with low complements C3, C4. Renal biopsy confirmed class III a+c lupus nephritis. She was managed with prednisolone, mycophenolate mofetil, hydroxychloroquine and ramipril. She responded well to treatment. She was admitted in August 2018 with recurrent abdominal pains, distension, diarrhoea, nausea, vomiting, 20kg unintentional weight loss, arthritis, lymphadenopathy, and peripheral oedema. Over the last 12 months, she had 5 admissions with similar GI symptoms, which were managed as viral gastroenteritis. Investigations showed nephrotic range proteinuria - urine PCR 330 (0-15 mg/mmol), low albumin = 27 (40-52 g/L), positive anti-dsDNA antibodies = 211 (0-10 IU/ml), CRP 7 (0-4 mg/L), ESR 44 (0-12 mm/hr) with low complements C3 0.36 (0.90-1.80 g/L) and C4 0.07 (0.10-0.40 g/L). Contrast enhanced computed tomography (CECT) scan of the abdomen revealed diffuse oedema of the large bowel extending from the splenic flexure to the rectum, several areas of small bowel thickening, peritoneal enhancement, and moderate volume ascites. Infective causes for colitis were ruled out including abdominal tuberculosis. Sigmoidoscopy and biopsy ruled out inflammatory bowel disease, whereas surgical and gastroenterology reviews ruled out other causes for her presentation. She was diagnosed with lupus enteritis with flare of lupus nephritis and managed with pulsed intravenous methylprednisolone followed by tapering high dose oral prednisolone. Her symptoms gradually improved, and she was discharged. Unfortunately, over the next month, she had recurrent admissions with flares of lupus enteritis requiring further intravenous methylprednisolone. As a result, she was commenced on monthly IV belimumab. Since starting belimumab, she has not had any further flares of lupus enteritis and her anti-dsDNA antibody and complements C3, C4 levels have normalised. Discussion Lupus enteritis (LE) presents with non-specific GI symptoms such as abdominal pain (most common), nausea, vomiting, diarrhoea and ascites. In most cases, it develops months to years after SLE diagnosis but in some cases, may be the presenting feature. Its pathogenesis remains unknown; however, mesenteric vasculitis and/or thromboses are thought to play a role. Contrast enhanced computed tomography (CECT) abdomen is the gold-standard investigation and usually shows bowel wall oedema, dilated bowel loops (&amp;gt;3 cm), bowel wall thickening with peripheral enhancement (“target sign”/”double halo sign”), engorgement of mesenteric vessels with a palisade pattern (“comb-sign”), increased attenuation of mesenteric fat and/or ascites. Laboratory investigations usually reveal markers of active lupus. Significant proteinuria (&amp;gt;0.5 g/24 h) is usually found in around 50% of patients. LE is very steroid responsive, with most patients achieving disease remission with steroids alone. Additional immunosuppression (such as cyclophosphamide, MMF, azathioprine, HCQ or rituximab) may be used concomitantly, for other manifestations of SLE or in those with relapsing or refractory disease. Belimumab has previously been licensed for use in SLE and lupus nephritis; however, there is sparse literature about its use in lupus enteritis. Our patient responded very well to belimumab, with both clinical and immunological remission. Key learning points • Lupus enteritis is a rare but severe gastrointestinal (GI) manifestation of SLE that presents with non-specific GI symptoms such as abdominal pain (most common), nausea, vomiting, diarrhoea and ascites. Clinicians managing SLE patients should have a high index of suspicion regarding the diagnosis, else it may be easily missed leading to recurrent admissions and delayed treatment. • Contrast enhanced CT abdomen is the gold-standard investigation and shows characteristic changes - bowel wall oedema, dilated bowel loops (&amp;gt;3 cm), bowel wall thickening with peripheral enhancement (“target sign”/”double halo sign”), engorgement of mesenteric vessels with a palisade pattern (“comb-sign”), increased attenuation of mesenteric fat and/or ascites • Lupus enteritis is very steroid responsive, with most patients achieving disease remission with steroids alone. Some patients with other SLE manifestations, or relapsing/refractory disease may require additional immunosuppression. Belimumab may be another option to consider in such patients.

P41 Decoding short stature in a child with lupus nephritis: an unusual association with de la Chapelle syndrome

Abstract Introduction Recent studies have implicated the dysregulation of epigenetic factors in maintaining favourable lyonization of X-chromosome as a plausible putative mechanism in causing high incidence of systemic lupus erythematosus (SLE) in females. This is reflected by the increased risk of SLE in patients with ‘disorders of sex development’ (DSD) such as Klinefelter’s syndrome (47,XXY). de la Chapelle syndrome (46,XX with SRY gene) is another DSD wherein patients resemble males phenotypically with 2 X-chromosomes in their karyotype. Herein, we report the diagnostic and therapeutic challenges in a case of juvenile-onset SLE with refractory lupus nephritis and concomitant association of de la Chapelle syndrome. Case description A 13-year-old boy presented with history of chronic febrile inflammatory polyarthritis involving small and large joints for 6-months. On examination, he had short stature, and swelling, tenderness and restriction of movement of the proximal and distal interphalangeal joints, wrist and shoulder joints of both sides. Investigations revealed elevated erythrocyte sedimentation rate with normal C-reactive protein. Routine urine microscopy examination was suggestive of proteinuria. Further immunological investigations revealed hypocomplementemia, positive anti-nuclear antibody (4+, homogeneous pattern) and elevated titres of anti-double stranded DNA. He was also noted to have positive direct coomb’s test and antiphospholipid antibodies. His renal biopsy was suggestive of lupus nephritis (Class II). Based on the above constellation of clinical and laboratory parameters, a diagnosis of SLE with lupus nephritis (Class II) and musculoskeletal involvement was proffered. He was started on oral prednisolone (2 mg/kg/day followed by taper), hydroxychloroquine (5 mg/kg/day) and sun protective measures. However, persistence of proteinuria after 3-months necessitated addition of mycophenolate mofetil (1200 mg/m2/day) following which his SLE-disease activity went into remission. Notwithstanding the control of SLE-disease activity, there was no improvement in his height after 1-year of follow-up. A pediatric endocrinology consultation for short stature revealed features of idiopathic growth hormone (GH) deficiency and primary hypogonadism. Chromosomal analysis was suggestive of 46,XX karyotype, and fluorescence in situ hybridisation revealed ‘XX’ pattern with SRY gene located on one of the X chromosomes. He was commenced on recombinant GH therapy for 18-months following which his height improved. At 2-years of follow-up, he developed worsening proteinuria. A repeat renal biopsy was suggestive of class-IV lupus nephritis. However, he responded poorly to 6-doses of monthly intravenous cyclophosphamide (500 mg/m2/dose). Considering refractory lupus nephritis, he was commenced on rituximab [(375 mg/m2/dose) at 0 and 2-weeks] following which his proteinuria became passive. He remains well on follow-up. Discussion SLE in DSD has been more frequently described in the context of Klinefelter’s syndrome (47, XXY), implicating the X chromosome as a putative mechanism in its pathogenesis. However, the clinical profile and outcome of SLE in patients with de la Chapelle syndrome has not been explored extensively. de la Chapelle syndrome (46, XX with SRY gene), first described in 1964, is a rare DSD with a reported prevalence of 1/20000 to 1/25000 newborn males. The clinical phenotype includes decreased body height, gynecomastia, maldescended testis and other features of hypogonadism including infertility. Chagnon et al reported the first patient of SLE in de la Chapelle syndrome. Authors described a 19-year-old man who presented with features of SLE since early childhood. His disease was complicated by severe rash, mucositis, arthritis, focal proliferative glomerulonephritis, transaminitis and refractory thrombotic thrombocytopenic purpura, and osteoporosis (including growth failure). In addition, he also had primary hypogonadism with normal GH. Dillon et al also reported another 46, XX male with presence of SRY gene. However, the clinical details including treatment were not elucidated in this paper. Both these patients were phenotypically male due to the presence of SRY gene, similar to the index patient. Our patient’s difficult clinical course with arthritis, growth failure and refractory lupus nephritis, and primary hypogonadism was similar to the patient reported by Chagnon et al. The treatment protocol of SLE in DSD is not well-established. Chagnon et al reported using corticosteroids, hydroxychloroquine, methotrexate, intravenous pulse cyclophosphamide, azathioprine, and plasmapheresis. The index patient was treated similarly; however, due to refractory lupus nephritis, he was also given rituximab. To the best of our knowledge, this is the first report of successful use of anti-CD20 therapy in SLE with DSD such as de la Chapelle syndrome. Key learning points • This case highlights the challenges in diagnosis and management of patients with DSD including de la Chapelle syndrome. The main learning point from this case was that short stature in juvenile-onset SLE in a boy with features of primary hypogonadism warrants further evaluation. As reported in previous literature, this subset of patients may not respond adequately to conventional first-line therapy. The need for escalation of therapy or primary therapy with rituximab in such patients needs further exploration. Another point of concern is using cyclophosphamide, a known drug to have adverse effect on testes, in these patients since it may further compromise testicular function.

OA24 Extended oligoarthritis with proximal muscle weakness and antinuclear antibody positivity associated with a novel genetic variant of uncertain significance in lipopolysaccharide-responsive and beige-like anchor protein (LRBA) gene

Abstract Introduction LRBA deficiency is associated with recurrent infections and immune dysregulation, particularly autoimmune cytopenias, enteropathy and intestitial lung disease, and in a few cases chronic polyarthritis and uveitis. Case description A girl presented at three years old with history of not walking for two months with no history of trauma or fever. Examination revealed arthritis in her ankles and knees. Ultrasound showed synovial thickening in both knees and small effusion to hips. There was no evidence of uveitis at presentation. Her bloods showed raised C-Reactive Protein (CRP) 33 mg/L and Erythrocyte Sedimentation rate (ESR) 45 mm/h. Anti-nuclear and anti-centromere antibodies were positive. Diagnosis was made of oligoarticular JIA and she was treated with intra-articular steroids in both knees and ankles and was started on oral prednisolone, weekly oral methotrexate. On subsequent clinic review, she had started to walk with mild restriction to internal rotation of hips and difficulty in getting up from sitting. She was started on regular hydrotherapy, physiotherapy and occupational therapy. From five to 11 years old, she had four flares of uveitis, treated with prednisolone eye drops; and two flares of arthritis, treated with steroids. Her methotrexate was changed to subcutaneous and at eight years of age she was also started on subcutaneous adalimumab fortnightly. Due to prolonged proximal muscle weakness, abnormal gait and chronic pain in leg joints without clinical or radiological evidence of synovitis during clinic reviews, she underwent thorough neurological work up which was inconclusive for myopathies. Her creatinine kinase levels, thyroid profile, MRI brain and spine were normal. Genetic work up showed two variants in the LRBA gene, one pathogenic and the other was variant of uncertain significance (VUS). Her CTLA4 expression was normal by flow cytometry. Discussion Three case reports have previously associated homozygous LRBA deficiency with polyarthritis. Compound heterozygous LRBA deficiency may present with various phenotypes including autoimmune disease affecting multiple organs, immune cytopenia and immune dysregulations including CTLA-4 expression. This report potentially widens the clinical spectrum of LRBA deficiency and given that it is a novel variant, prompts us to screen for this gene mutation in patients with JIA where remission is challenging and there is a need for continuous immunosuppressive or immune-modulatory therapy. Three case reports have previously associated homozygous LRBA deficiency with polyarthritis. Compound heterozygous LRBA deficiency may present with various phenotypes including autoimmune disease affecting multiple organs, immune cytopenia and immune dysregulations including CTLA-4 expression. This report potentially widens the clinical spectrum of LRBA deficiency and given that it is a novel variant, prompts us to screen for this gene mutation in patients with JIA where remission is challenging and there is a need for continuous immunosuppressive or immune-modulatory therapy. Three case reports have previously associated homozygous LRBA deficiency with polyarthritis. Compound heterozygous LRBA deficiency may present with various phenotypes including autoimmune disease affecting multiple organs, immune cytopenia and immune dysregulations including CTLA-4 expression. This report potentially widens the clinical spectrum of LRBA deficiency and given that it is a novel variant, prompts us to screen for this gene mutation in patients with JIA where remission is challenging and there is a need for continuous immunosuppressive or immune-modulatory therapy. Key learning points • There is no single diagnostic investigation for JIA as the aetiology is complex and there are currently no specific clinical guidelines of when to consider genetic testing in patients with JIA. With the mainstreaming of genetic services and improved access to cheaper, advanced next-generation sequencing, we should consider looking into monogenic conditions that mimic JIA. • The case illustrates the challenges of determining whether VUS are pathogenic in causing arthritis, or just incidental findings. Compound heterozygous LRBA may present within a spectrum of clinical features, further analysis with CTLA4 expression by flow cytometry and genetic analysis of siblings and parents will be helpful. • Compound heterozygous LRBA variation has different clinical manifestation which needs personalised treatment. Treatment with abatacept (a soluble CTLA4 immunoglobulin fusion protein) which is reported in a case series of LRBA deficiency. Risks of continuous immunosuppressive treatment need to be balanced with more definitive hematopoietic stem cell transplantation (HSCT) previously used to achieved complete remission in LRBA deficiency.

Clinical characteristics, treatment and outcome of subacute cutaneous lupus erythematosus induced by PD-1/PD-L1 inhibitors.

PD-1/PD-L1 inhibitors have increasingly been associated with the occurrence of subacute cutaneous lupus erythematosus (SCLE), but the clinical characteristics and outcomes remain under-explored. Literature on PD-1/PD-L1 inhibitors induced SCLE was retrieved from Chinese and English databases until June 31, 2024, and clinical data of patients were extracted for retrospective analysis. Twenty-nine patients participated, with a median age of 63 years (range 43, 80). The most frequently reported drugs were Nivolumab (51.7%) and pembrolizumab (31.0%). The median time from treatment initiation to SCLE onset was 3 months (range 0.5, 47). Cutaneous manifestations presented primarily as papulosquamous lesions (65.5%) and erythema annulare (31.0%), predominantly occurring on the trunk (51.7%) and arms (51.7%). Serological analysis revealed positive anti-Ro antibodies in 91.7% of patients, positive antinuclear antibodies in 75.0%, and positive anti-La antibodies in 50.0%. Skin biopsies showed interface dermatitis in 65.5% of cases and lymphocyte infiltration in 82.8%. Treatment with topical corticosteroids, systemic corticosteroids, and hydroxychloroquine led to gradual improvement or resolution of the rash, with a median recovery time of 1 month (range 0.5, 11). As the use of PD-1/PD-L1 inhibitors in oncology increases, SCLE should be recognized as a rare cutaneous adverse effect. Histological and serological evaluations play a critical role in diagnosing SCLE. Typically, SCLE resolves on its own with appropriate local and systemic treatment.

Screening for comorbid autoimmune disease should be considered in children with ANA positive juvenile idiopathic arthritis – results from the south-Swedish juvenile idiopathic arthritis cohort

BackgroundThere is no consensus or clinical guidelines for screening routines of autoimmune disease in individuals with juvenile idiopathic arthritis (JIA), since results are conflicting whether the risk for such conditions is increased or not among individuals with JIA. The aim of this study was to investigate if the frequency of comorbid autoimmune conditions is increased after JIA diagnosis in a validated population-based JIA cohort in southern Sweden.MethodsAutoimmune comorbidities were evaluated in a pre-existing population-based JIA cohort of 302 participants, constituting of individuals diagnosed with a validated JIA diagnosis 2000–2010 in southern Sweden. The comorbidities were determined through analysis of diagnosis codes registered after the JIA diagnosis and until 2019. With the use of a reference population of 1510 age- and sex matched individuals, hazard ratios (HR) were calculated with Cox proportional models.ResultsDuring the study period, 7.7% of the JIA cohort received an autoimmune diagnosis after their JIA diagnosis. Individuals with JIA had an increased risk of autoimmune diseases in general (HR 4.11, 95% CI 2.13–7.91) within the first 7 years of disease, as well as separately for coeliac disease (HR 5.24, 95% CI 1.76–15.65) and hypothyroidism (HR 3.74, 95% CI 1.14–12.30) compared to the reference population. Antinuclear antibody (ANA) positivity was associated with a significantly increased risk of comorbid autoimmune disease in the JIA cohort, with HR 6.21 (95% CI 1.64–23.55) for ANA positive individuals.ConclusionsIndividuals with JIA have a significantly increased risk of being diagnosed with an autoimmune condition after receiving their JIA diagnosis compared to matched references. ANA positivity is associated with a further increased risk. Our results emphasize awareness in physicians of additional autoimmune disorders in individuals with JIA and advocate serological screening of autoimmune conditions during follow-up.

ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients: Results from the APS ACTION Clinical Database and Repository.

This study focused on the prevalence and impact of antinuclear antibodies (ANA) in antiphospholipid antibody (aPL)-positive patients without concomitant systemic autoimmune rheumatic diseases (SARDs). Data from aPL-positive patients with or without Revised Sapporo APS classification criteria were retrieved from the APS ACTION Registry. Patients with concomitant SARDs were excluded. 430 aPL-positive patients were included in the analysis, 56% ANA-positive and 44% negative. ANA positivity was significantly associated with history of hematologic manifestations (persistent autoimmune hemolytic anaemia, thrombocytopenia, leukopenia and/or lymphopenia) (16% of ANA-positive vs 7% of ANA-negative, p= 0.006). Triple aPL-positivity was more frequent in the ANA-positive subgroup (p= 0.02), along with low baseline C3 and C4 levels (p= 0.05 and p= 0.009, respectively), and higher frequency for extractable nuclear antigens (ENA). Among aPL-positive patients with no APS classification, ANA-positive patients showed a higher rate of arthritis (p= 0.006). Among female patients who have experienced at least one pregnancy, 113 were ANA-positive and 96 were ANA-negative; ANA-negative patients had a higher number of pregnancies (p= 0.018), and number of live births (p= 0.014). A wider proportion of ANA-positive patients were treated with hydroxychloroquine (HCQ) (p< 0.001). When we analysed aPL-positive patients with no other SARDs, ANA status was not associated with thrombosis or pregnancy morbidity. Interestingly, ANA-positive patients showed higher rates of systemic autoimmune features, including hematologic manifestations, multiple aPL positivity, lower complement levels, ENA positivity, and joint involvement, and were more often treated with HCQ. Finally, aPL-positive subjects who were ANA-negative had a higher rate of pregnancies and live births.

Mitigating overuse of antinuclear antibody (ANA) testing through educational intervention: a study in internal medicine and neurology departments.

Overuse of antinuclear antibody (ANA) tests leads to increased costs, false positives, and unnecessary treatments. This study evaluated ANA overuse in internal medicine and neurology departments and assessed the impact of an educational intervention. This quality improvement educational intervention study examined ANA test overuse in five internal medicine departments and one neurology department at a university-affiliated medical center. The educational intervention included a session focusing on ANA testing appropriateness. Outcome measures comprised the ANA/new patient ratio (APR) and the percentage of positive ANA test results. Outcomes were compared between the pre- and post-intervention periods (both 6months). The intervention took place in December 2021. The APR decreased from 43% in the pre-educational intervention period to 27% in the post-intervention period in the neurology department (odds ratio [OR] 0.49, confidence interval [95% CI] 0.37-0.63, P < 0.0001) and from 2.6% to 2.2% in the internal medicine departments (OR 0.89, 95% CI 0.73-1.10, P = 0.28). The percentage of positive ANA tests increased from 43% pre-intervention to 53% in the post-intervention period (OR 1.49, 95% CI 0.90-2.46, P = 0.12) in the neurology department and from 48% to 59% (OR 1.56, 95% CI 0.99-2.44, P = 0.0543) in the internal medicine departments. A simple educational intervention reduced unnecessary ANA testing in the neurology department but not in internal medicine departments, improving patient selection and potential cost savings. The results underscore the importance of targeted education to promote evidence-based behavior among healthcare professionals. Further research with longer follow-up is needed to assess the sustainability of these improvements.

A Clinicopathological Analysis of Membranous Nephropathy and Its Correlation With the Immunohistochemical Expression of Phospholipase A2 Receptor (PLA2R) in Renal Biopsies in a Tertiary Care Center.

Background Membranous nephropathy (MN) is the second most common adult-onset nephrotic syndrome worldwide. Traditionally, these were classified as primary and secondary, with primary causes showing higher positivity for various antigens, includingM-typephospholipase A2 receptor (PLA2R), a key antigen located in the podocyteagainstwhich antibodies are directed. Aim The aim of this study is to analyze the cases diagnosed as MN with clinicopathological parameters and PLA2R positivity by immunohistochemistry in renal biopsies. Methods A retrospective observational study of 65 cases of MN diagnosed in renal biopsiesby light microscopy and confirmed by ancillary studies from the Department of Pathology, Sri Ramachandra Medical College and Research Institute over a period of three years (2021-2023). The demographic profile and patient details were obtained from the hospital information system and archival case files.The description of categorical variables was expressed as frequency and percentage. The Chi-squared test and Fisher's exact test were employed to compare the distribution of qualitative variables between the groups. Results This case study includes 65 membranous nephropathy cases, of which 47.7% were diagnosed as primary MN and 52.3% as secondary MN. Of these, serum antinuclear antibody (ANA) positivity was seen in 80.6% of cases of primary MN and 58.8% of cases of secondary MN. Elevated serum C3/C4 levels were noted in 51.6% of primary MN and 47.1% of secondary MN (Ref. C3 = 90-180mg/dl; C4 = 10-40mg/dl). Immunofluorescence for IgG showed a nonspecificassociation between primary and secondary MN. Immunohistochemistry (IHC) for PLA2R showed positivity in 72.3% of primary MN cases and 27.7% of secondary MN cases. The Chi-squared test and Fisher's exact test showed statistical significance for these parameters. Conclusion This study signifies that primary MN is more frequently associated with positive immunohistochemical expression of PLA2R. These findings help in characterizing these cases as antigen-specific and have helped in the ongoing validation ofPLA2R IHC as a diagnostic marker, which aids in monitoring the disease progression, remission, and recurrence. Despite the availability ofvarious modalities for estimating the levels of anti-PLA2R, diagnostic challenges persist. Hence, most renal laboratories continue to adopt renal biopsy stainingfor IHC PLA2R to identify and monitor the disease progression.

Multifocal osteonecrosis due to the synergistic impact of inherited thrombophilia, autoimmunity and pregnancy: a case report.

Multifocal osteonecrosis is a rare entity which can lead to bone fragility, fractures and considerable morbidity. The objective of this report is to describe the presentation, evaluation and management of a case of multifocal osteonecrosis. A 34-year-old lady presented with multiple fractures and bone pain which was exacerbated during pregnancy. She was found to have osteonecrosis involving multiple sites. Investigation revealed that she had an undefined autoimmune condition with antinuclear antibody and anti-Ro (SS-A) positivity, not fulfilling criteria for diagnosis of Sjogren syndrome. She had low Protein S levels for age and gender (confirmed on 2 occasions 12 weeks apart outside pregnancy). She had a novel variant in the PROS1 gene (NM_000313.4:c.1513G>A; p.Gly505Ser) which is associated with heterozygous Protein S (PS) deficiency. She had a good response to treatment with anticoagulation. The combination of inherited thrombophilia, autoimmunity and the thrombophilic state induced by pregnancy probably contributed to the severe phenotype in this patient. The variant was identified in the Lamin G1 domain, which is instrumental in PS binding to tissue factor pathway inhibitor and C4 binding protein, thus playing a role in both the coagulation and complement pathway, and could explain the coexistence of autoimmunity with thrombophilia. This variant is present in 0.034% of South Asians in the gnomAD population database, and may represent an important cause of inherited thrombophilia in this group.

Systemic Lupus Erythematosus, An Unusual Presentation: A Case Report In Azal Hospital, Sana’a, Yemen

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by various clinical presentations and potential involvement of multiple organ systems; it exhibits a significant female predominance, with a peak incidence of middle-aged individuals. In this article, we report a case of a 19 years old female patient who presented with fever, headache, fatigue and neck stiffness. Initial investigations revealed a normal white blood cell count (WBC) with neutrophilia, leading to a diagnosis of bacterial meningitis. The patient responded to antibiotic and analgesic treatment. However, subsequent development of arthritis and skin lesions raised suspicion of systemic lupus erythematosus, which was confirmed by positive anti-dsDNA and antinuclear antibody (ANA) tests.

Clinical Features and Electroencephalogram Analysis ofBrain Network Functional Connectivityin Anti-Leucine-RichGlioma-Inactivated1Antibody Encephalitis.

To summarize the clinical manifestations, laboratory findings, and magnetic resonance imaging (MRI) characteristics of anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis (anti-LGI1 antibody encephalitis) and explore the electroencephalogram (EEG) features. We retrospectively analyzed the medical history of 16 patients diagnosed with anti-LGI1 antibody encephalitis at the First Hospital of Hebei Medical University from 2021 to 2023. EEGs of patients with anti-LGI1 antibody encephalitis and healthy individuals were analyzed. Based on Video-EEG signal analysis of EEG δ, θ, α, β frequency bands, weighted phase lag index values were calculated to form brain network matrices, studying differences in coherence between brain regions of patients with anti-LGI1 antibody encephalitis and healthy individuals. Patients with anti-LGI1 antibody encephalitis often presented with subacute onset seizures and cognitive decline. Routine test of cerebrospinal fluid was mostly normal. Serum testing revealed hyponatremia in 62.50% of patients, along with positive serum antinuclear antibodies, decreased vitamin B12, and abnormal cytokines such as interleukin-6. Head MRI revealed abnormal lesions related to the disease in seven cases (43.75%), mainly located in the unilateral or bilateral frontal and temporal lobes of the hippocampus. The EEG mainly showed generalized and focal slow waves, sometimes with focal discharges. Brain network functional connectivity analysis found a significant weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands. Intravenous pulse corticosteroids and intravenous immunoglobulin are first-line immunotherapies for anti-LGI1 antibody-related encephalitis. The disease recovery and cognitive decline improved in most patients. Anti-LGI1 antibody encephalitis is characterized by seizures and cognitive dysfunction. Serum may show abnormalities in immune indicators such as cytokines. Head MRI mainly reveals abnormal signals in the frontal-temporal lobes and the hippocampus. EEG brain network connectivity analysis reveals characteristic weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands.

Safety and Efficacy of Durvalumab After Chemoradiotherapy in Antinuclear Antibody-positive Patients With Non-small Cell Lung Cancer.

Pneumonitis during durvalumab consolidation therapy after chemoradiotherapy (CRT) is a major cause of treatment discontinuation. Although previous studies have revealed an association between antinuclear antibody (ANA) positivity and the safety and efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC), there are no reports on durvalumab consolidation therapy. This study investigated the safety and efficacy of durvalumab after CRT in ANA-positive patients. We retrospectively reviewed patients with unresectable NSCLC treated with durvalumab after CRT between August 2018 and July 2022 at our institution. We evaluated the association among ANA positivity, treatment-related adverse events (AEs), and survival outcomes. Overall, 80 patients were enrolled, 39 of whom were ANA-positive. Although there were no significant differences in the incidence of each AE of any grade, ANA-positive patients tended to have a higher frequency of pneumonitis of grade 3 to 5 than ANA-negative patients (12.8% vs. 2.4%, p=0.104). ANA-positive patients had a significantly shorter median progression-free survival (PFS) and overall survival (OS) than ANA-negative patients [14.9 months vs. not reached (NR), p=0.005; NR vs. NR, p=0.013]. Multivariate analysis revealed that ANA positivity was an independent predictor of shorter PFS (HR=2.23; 95% CI=1.16-4.29; p=0.016) and OS (HR=2.28; 95% CI=1.01-5.12; p=0.046). ANA-positive patients receiving durvalumab after CRT tended to have a higher frequency of severe pneumonitis and significantly worse PFS and OS compared with ANA-negative patients.

Detection and differentiation of antinuclear antibodies in serum of dengue suspected patients with or without systemic autoimmune disease in Kolkata, India

ABSTRACT The pathophysiology of dengue may be influenced by antibodies released during infection. Several autoimmune diseases are accompanied by antinuclear antibodies (ANAs) but 8–10% of the general population have positive ANA tests. To test the hypothesis that an ANA-positive test indicates an immune dysregulated state that modifies the risk for certain clinical disorders in people with or without an autoimmune disease, we examined the various ANA profiles and their relationships to various autoimmune disorders, as well as the severity of these relationships, in patients infected with dengue fever. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) methods were used. Indirect immunofluorescence assay (IIFA) and line immunoassay (LIA) were performed to detect and differentiate the ANAs among dengue infected patients. Out of 135 dengue virus-positive patients, 94.07% were positive by ELISA and 5.93% positive by RT-PCR method. ANAs by IIFA and LIA were detected in 54.8% and 18.5% of the dengue positive patients, respectively, and 10.3% and 7.1% of the 126 dengue negative patients, respectively. This study showed that dengue was associated with an increased risk of autoimmune myositis and mixed connective tissue disease (MCTD), a rare complication of dengue. The risk of other autoimmune diseases did not seem to increase after DENV infection.

A Case Report of Mixed Connective Tissue Disease Predominantly Manifesting as Systemic Sclerosis in a Middle-Aged Nepali Woman

Introduction: Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disorder, first described in 1972, that presents with overlapping features of systemic lupus erythematosus, systemic sclerosis, and polymyositis. The diagnosis of MCTD is complex and often delayed due to its varied clinical manifestations and the requirement of serological confirmation, particularly the presence of anti-U1 RNP antibodies. Despite its global prevalence, data on MCTD are limited, especially in the South Asian population.  Case Report: We present the case of a 42-year-old Nepali woman with a decade-long history of myalgia, muscle weakness, and joint pain, initially misdiagnosed as rheumatoid arthritis. Over time, she developed Raynaud phenomenon, dysphagia, and progressive muscle weakness, which prompted further investigation. Serological testing revealed elevated levels of anti-U1 RNP antibodies and a positive antinuclear antibody (ANA) titer, confirming the diagnosis of MCTD according to the Alarcón-Segovia criteria. The patient was successfully managed with a regimen of corticosteroids, hydroxychloroquine, and nifedipine, resulting in significant symptomatic improvement.  Discussion: This case underscores the diagnostic challenges associated with MCTD, a condition that may present with nonspecific symptoms and mimic other rheumatic diseases. The prolonged diagnostic journey of this patient highlights the need for heightened clinical suspicion and comprehensive serological testing in patients with overlapping connective tissue disease features. Furthermore, the case contributes to the limited body of literature on MCTD in the South Asian population, emphasizing the importance of early recognition and tailored management strategies to improve patient outcomes.  Conclusion: MCTD is a complex and under-recognized autoimmune disorder, particularly in the South Asian context. This case report highlights the importance of considering MCTD in the differential diagnosis of patients with multi-systemic involvement and underscores the role of serological testing in confirming the diagnosis. Early diagnosis and appropriate management are crucial in mitigating disease progression and improving the quality of life for patients with MCTD.

Performance of the Systemic Lupus Erythematosus Risk Probability Index (SLERPI) in a cohort of Colombian population

ObjectiveTo evaluate the performance of the Systemic Lupus Erythematosus Risk Probability Index (SLERPI) in Colombian patients with systemic lupus erythematosus (SLE).MethodsThe Colombian cohort included 435 SLE patients and 430 controls with other autoimmune diseases (ADs). Clinical and serological data were collected, and SLE was indicated by SLERPI scores > 7. The American College of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012, and European League Against Rheumatism (EULAR)/ACR-2019 criteria were used as reference standards. The impact of overt polyautoimmunity (PolyA) on SLERPI performance was assessed. Additionally, multivariate lineal regression analysis was performed to evaluate the contribution of SLERPI features to the overall SLERPI score.ResultsSLE patients had higher SLERPI scores (P < 0.0001), with almost 90% meeting "definite" lupus criteria. Main factors influencing SLERPI included immunological disorder (β:44.75, P < 0.0001), malar/maculopapular rash (β:18.43, P < 0.0001), and anti-nuclear antibody positivity (β:15.65, P < 0.0001). In contrast, subacute cutaneous lupus erythematosus/discoid lupus erythematosus (β:2.40, P > 0.05) and interstitial lung disease (β:-21.58, P > 0.05) were not significant factors to the overall SLERPI score. SLERPI demonstrated high sensitivity for SLE, both for the overall SLE group and for those without overt PolyA (95.4% and 94.6%, respectively), but had relatively low specificity (92.8% and 93.7%, respectively). The model showed high sensitivity for hematological lupus (98.8%) and lupus nephritis (96.0%), but low sensitivity for neuropsychiatric lupus (93.2%). Compared to the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria, SLERPI yielded the highest sensitivity and lowest specificity.ConclusionSLERPI efficiently identified SLE patients in a Colombian cohort, showing high sensitivity but low specificity. The model effectively distinguishes SLE patients, even in the presence of concurrent overt PolyA.Key Points•SLERPI has a high sensitivity, but low specificity compared to ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria in the Colombian population.•Within the SLERPI score, immunological disorder, malar/maculopapular rash, and anti-nuclear antibody positivity are the strongest predictors of SLE.•SLERPI model can efficiently distinguish patients with SLE, regardless of concomitant overt PolyA.•SLERPI demonstrates high sensitivity in identifying hematological and nephritic subphenotypes of SLE.

Antinuclear Antibodies in Systemic Lupus Erythematous – Their Complex Role and Clinical Significance in Diagnosis

Antinuclear antibodies (ANA) are a wide group of proteins directed against autologous cellular components, primarily nucleic acids and histones. Their levels are assessed using immunofluorescence on Hep-2 cells or a solid-phase ANA screening immunoassay to subsequently obtain titer value with positive cut-point of ≥1:80. Studies show that ANA can be found in 13% of general population, but typically they are associated with autoimmune conditions and inflammatory connective tissue diseases for example: systemic lupus erythematosus (SLE), sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, juvenile idiopathic arthritis, systemic sclerosis, inflammatory myopathies. ANA detection is especially important for SLE, where 2 antibody types - anti-Sm and anti-dsDNA - serve as an entry diagnostic criterion. With increasing patient screening for those antibodies, it is important to determine that alone, positive ANA assays cannot confirm nor deny any disease and to classify their presence as a marker of a disease it is required to satisfy additional additive criteria approved in 2019 by European League Against Rheumatism/American College of Rheumatology. SLE diagnosis can be made when patient collects 10 points from clinical or immunologic domains described by EULAR/ACR, which makes SLE diagnosis challenging and therefore, describing the guidelines is vital to remain cautious about overestimation of the position positive ANA values hold in clinical practice.In conclusion the positive ANA test may be a basis for diagnosis, when additional symptoms occur, but alone does not hold any diagnostic significance and may lead to unnecessary stress for patient.

Clinical analysis of maternal autoantibody-mediated complete left bundle branch block in 9 children

Objective: To analyze the clinical characteristics, treatment, and outcomes of children with complete left bundle branch block (CLBBB) mediated by maternal autoantibodies. Methods: A retrospective analysis was conducted on nine children diagnosed with maternal autoantibody-mediated CLBBB, treated at Beijing Anzhen Hospital and Fujian Provincial Hospital from March 2015 to August 2023. Their clinical characteristics, electrocardiographic and echocardiographic findings before and after treatment were reviewed. Paired sample t-test was used for inter-group comparison. Results: Among the mothers, 6 had positive antinuclear antibodies (ANA), 5 had anti-Sjogren syndrome antigen A antibodies, and 3 had anti-Ro-52 antibodies. The cohort included one female and eight male children, diagnosed with CLBBB at the age of 1 (2, 13) months. The positive autoantibodies in the infants, consisted with maternal antibodies, were detected within the first 3 months of life among 3 cases. Treatments included anti-heart failure therapy, myocardial nutritional support, intravenous immunoglobulin (IVIG) and glucocorticoids. Before treatment, the levels of troponin I (0.175 (0.060, 10.270) μg/L) and N-terminal pro-B-type natriuretic peptide (420 (327, 12 865) ng/L) were elevated, which normalized in most cases after treatment. Post-treatment, the QRS duration significantly shortened compared to pre-treatment ((137±15) vs.(169±25) ms, t=3.76, P<0.001), and the QTc interval significantly decreased ((433±41) vs. (514±27) ms, t=4.95, P=0.001). Before treatment, varying degrees of mitral and tricuspid regurgitation and marked interventricular septal dyskinesia were observed in echocardiography. After treatment, valve regurgitation and ventricular septum motion significantly improved, with a marked increase in left ventricular ejection fraction ((51±13)% vs. (27±6)%, t=-6.66, P<0.001). Conclusions: Maternal autoantibody-mediated CLBBB in children presents with chronic heart failure in infancy. Early treatment with anti-heart failure medications, IVIG and glucocorticoids can improve clinical symptoms.