Nuclear Antibodies Research Articles

The role of tribbles homolog 2 in vascular smooth muscle cell proliferation.

Tribbles homolog 2 (TRIB2) functions as an adapter protein that regulates signal transductions involved in a variety of cellular functions, including tumorigenesis. However, the role of TRIB2 in the proliferation of vascular smooth muscle cells (VSMCs) and the underlying expression mechanisms remain unclear. The present study investigated the role of TRIB2 in VSMC proliferation and revealed that TRIB2 expression increases following vascular injury and platelet-derived growth factor (PDGF)-BB-stimulated VSMCs. We found that pretreatment with diphenyleneiodonium (a nicotinamide adenine dinucleotide phosphate oxidase inhibitor), U0126 (an inhibitor of mitogen-activated protein kinase kinase 1 [MEK1]), or siRNA targeting the gene encoding early growth response 1 (EGR-1) significantly inhibits PDGF-BB-induced TRIB2 expression in VSMCs. Furthermore, TRIB2 knockdown significantly inhibits PDGF-BB-induced proliferation of VSMCs but does not affect the phosphorylation of AKT. However, phosphorylation of ERK1 and expression of proliferating cell nuclear antibody are significantly suppressed in VSMCs by PDGF-BB stimulation. Thus, PDGF-BB-induced TRIB2 expression is mediated by ROS/ERK/EGR-1 pathways and plays a critical role in VSMC proliferation via modulation of ERK activity. We propose TRIB2 as a promising therapeutic target for the prevention of neointima formation and vascular disease.

Long-term presence of autoantibodies in plasma of cured leprosy patients

Autoantibodies have been detected in leprosy patients, indicating that infection with M. leprae may lead to autoimmune disorders. However, whether autoimmune response last until patients are cured is unknown. Knowing the autoimmune response in cured leprosy patients is essential to identify whether symptoms are caused by leprosy itself or by other immune-related diseases. This knowledge is essential for the ongoing health management in cured leprosy patients where autoimmune disorders still exist. In our study, we selected six autoantibodies, including anticardiolipin antibody of IgG (ACA), anti-nuclear antibody (ANA), extractable nuclear antigen antibody (ENA), anti-streptolysin O (ASO), anti-double stranded DNA antibody (dsDNA), and rheumatoid factor (RF), that had been reported in leprosy patients as typical autoantibodies. We tested the six typical autoantibodies combined with LACC1, which encodes a protein associated with autoimmune disease such as Crohn’s disease and is also the susceptible gene conferring leprosy risk, in cured leprosy patients through ELISA to assess the cured patient’s immune status. We observed high positive rates of autoantibodies in cured leprosy patients, and the average plasma levels of five (ACA, ANA, ENA, ASO, and RF) out of the six autoantibodies were significantly higher in cured leprosy patients than in controls. The positive detection of autoantibodies is independent of the recovery period. Moreover, the level of these autoantibodies showed a strong positive correlation with the level of LACC1 in both controls and cured patients. This study showed that there is long-term autoimmunological activation in leprosy patients, even after decades of recovery. Autoimmune responses may influence the development and prognosis of leprosy. Special care should be given to posttreatment or cured leprosy patients regarding long-term autoimmunological activation.

Study of the correlation between Nailfold capillaroscopic changes and the new potential biomarker of lupus nephritis activity

Background: In the past, researchers have looked for a variety of blood and urinary indicators for lupus nephritis (LN) in the hopes of identifying one that accurately reflects disease activity. Urinary alpha one antitrypsin is a new potential biomarker in detection of lupus nephritis which was discussed in this research. Capillaroscopic alterations have been shown to correlate with disease activity, including LN, suggesting that they may be helpful in assessing disease severity.Methods: Fifty individuals with SLE (as determined by the Systemic Lupus Erythematosus Disease Activity Index; SLEDAI) who also had at least six nailfolds suitable for microscopic evaluation participated in the research. Complete blood count (CBC), serum creatinine, and other diagnostic tests: blood urea and eGFR, Erythrocyte Sedimentation Rate (ESR), diagnostic marker for lupus (Anti –Nuclear Anti body (ANA), Anti-ds- DNA and Serum complement level (C3&C4), 24-hour urinary protein, complete urine analysis and urinary alpha one antichymotrypsin using ELISA technique in addition to nailfold capillaroscopic changes test (NFC).Results: Comparison between the normal and minor change group and between normal and major change group according to Urinary ALPH 1ACT, SLE activity, cutaneous manifestation showed high statistical significance p<0.001. There was Strong positive significant correlation between cases with SLE activity and had capillarscopic changes and high Urinary ALPH 1ACT. There was Strong positive significant correlation between urinary ALPH 1ACT, serum creatinine and 24HR urinary proteins.Conclusions: Urinary ALPH 1ACT is new potential biomarker of lupus nephritis, it was elevated in active SLE cases particularly active lupus nephritis and also with cases with capillaroscopic changes.

The risk of development of primary biliary cholangitis among incidental antimitochondrial M2 antibody-positive patients.

This study investigated the risk of the development of primary biliary cholangitis (PBC) in individuals who were incidentally identified as having positive antimitochondrial antibodies (AMA)-M2. We retrospectively reviewed extractable nuclear antibody (ENA) panel test results to identify the incidental AMA-M2-positive patients. Patients who filled the diagnostic criteria for PBC were excluded. AMA-M2-positive patients were further evaluated by physical examination, liver biochemistry, liver ultrasonography, and transient elastography (TE) and were also closely followed. We included 48 (n=45, 93% female) individuals with a median age of 49 (range: 20-69) years. The median follow-up duration was 27 months (range: 9-42) after the detection of AMA-M2. Thirty-three (69%) patients had concomitant autoimmune/inflammatory disorders. Twenty-eight (58%) individuals showed seropositivity for ANA, and 21 had (43%) positive AMA. Fifteen (31%) patients developed typical PBC according to the international PBC diagnostic criteria during the follow-up, and five of them (18%) had significant fibrosis (≥8.2 kPA) by TE at the time of PBC diagnosis. Two-thirds of the incidental AMA-M2-positive patients developed typical features of PBC after a median 27-month follow-up. Our results suggest that AMA-M2 patients should be closely followed up to detect the late development of PBC.

An Unusual Case of Intermittent Fever With Multiple Liver Lesions

Question: A 46-year-old man with a history of hypertension presented to our hospital with a chief compliant of intermittent fever for 2 weeks. He denied a history of nausea, vomiting, abdominal pain, diarrhea, abdominal distention, loss of appetite, or weight loss. Physical examination on admission was unremarkable. Laboratory studies showed white blood cells 15.32 × 109/L (reference 3.5–9.5 × 109/L) with 38.3% (reference 0.4%–8.0%) eosinophils, C-reactive protein 49.72 mg/L (reference 0–10 mg/L), and erythrocyte sedimentation rate 44 mm/h (reference 0–15 mm/h). No parasite eggs or larvae were found in microscopic examination of direct smears of the stool. Liver function tests revealed alanine transaminase 50.5 IU/L (reference 9–50 IU/L), alkaline phosphatase 134 IU/L (reference 15–40 IU/L), gamma-glutamyltransferase 224 IU/L (reference 10–60 IU/L), total protein 40.1 g/L (reference 65–85 g/L), and albumin 21.6 g/L (reference 40–55 g/L). His renal function and tumor markers, such as alpha-fetoprotein, carcino-embryonic antigen, and carbohydrate antigen 19-9 were all within normal ranges. Tests for hepatitis B, hepatitis C, antinuclear antibodies, extractable nuclear antigen antibodies, and anti–neutrophil cytoplasm antibodies were all negative. No significant abnormalities were detected on electrocardiography, echocardiography, and chest computed tomography (CT). Routine ultrasound revealed multiple hypoechoic areas with unclear borders in the left lobe and right posterior lobe of the liver. Magnetic resonance imaging (MRI) of the liver was subsequently performed and showed multiple nodular or clumpy lesions as low signal intensity on T1-weighted imaging (WI) (Figure A) and high signal intensity on fat-suppressed T2-WI (Figure B) and diffusion WI (Figure C). Contrast-enhanced scan exhibited slightly heterogeneous enhancement (Figure D) or annular enhancement (Figure E). MRI did not indicate any anatomic malformations or intrahepatic or extrahepatic bile duct dilation. Positron emission tomography–computed tomography (PET-CT) revealed increased 18F-fluorodeoxyglucose uptake in the liver lesions (maximum standardized uptake value 3.8–5.2) (Figure F). The patient subsequently underwent CT-guided liver biopsy. Histopathology demonstrated chronic hepatic inflammation with prominent eosinophilic infiltration in portal areas and some acinar areas (Figure G).

Resolvins Modulate Netosis and Autoimmunity in Sickle Cell Disease

Sickle cell disease (SCD) is a genetically determined hematological disease which is characterized by anemia, chronic hemolysis, and multi-organ chronic inflammatory vasculopathy with acute vaso-occlusive painful crises and chronic organ damage. The pathophysiology of SCD is complex and involves several other cell types and metabolic pathways than erythrocytes, including neutrophils and soluble factors such as cytokines or alternative complement pathway which affect the function of vascular endothelium. An inflammatory vasculopathy with chronically activated neutrophils releasing Neutrophil Extracellular Traps (NETs) is a key component of the pathophysiology of sickle cell disease (SCD). Chiang et al. have recently shown that resolvins (Rv) reduce NETS and improve NETs clearance in a model of sepsis by Staphylococus aureus, a known trigger of NETosis (Chiang N et al. Blood 139 (8): 1222, 2022). We previously reported that targeting pro-resolution mechanisms with Rv improves SCD vasculopathy and organ damage in humanized sickle mice. Here, we studied 23 adult patients with SCD, followed by the Comprehensive center for hemoglobinopathies and rare anemias, University of Verona and AOUI Verona from January 2019 to December 2021. For each patient the presence/absence of concomitant rheumatological condition such as rheumatoid arthritis, other inflammatory arthropathies, immune-mediated dermatological conditions, Sicca syndrome and Raynaud's phenomenon, were assessed. Eight age, and ethnicity matched healthy controls were analyzed. Blood was collected for hematological and biochemical assay as part of the standard clinical care for these patients. Additional blood was collected for research studies on whole blood and on plasma cytokines. SCD patients display significant increase in tumor- necrosis-factor (TNF)- α (p = 0.011) and interleukin (IL)-10, suggesting both active inflammatory state and an upregulated counterregulatory mechanism to limit inflammation. We observed that antinuclear antibodies (ANA), but not extractable nuclear antibodies (ENA), were significantly increased in SCD patients (provide specific data here). Previous reports have reported the presence of this type of autoantibodies in the absence of autoimmune clinical manifestations in patients with SCD (Toly-Ndour C et al J Rheumatol 38: 302, 2011). ANA+ SCDsubjects (defined by a cell nuclei homogenous pattern, and positive dilution in the 1:80 to 1: 160 range) had a higher inflammatory and hemolytic status, as demonstrated by increased WBC and neutrophil counts and LDH values compared to ANA- subjects. NETosis plays a key role in modification and externalization of autoantigens involved in production of autoantibodies such as ANA. Here, we found basal NETosis was higher, though not significant, in ANA+ SCD subjects compared to ANA-SCD patients. This was associated with lower expression of receptors for RvD1 and D2, namely ALX, GPR32/DRV1, and GPR18/DRV2 on PMN, monocytes, and lymphocytes from ANA+ SCD patients when compared to ANA- SCD subjects, who were also characterized by relatively low LDH compared to ANA+ SCD patients. Exogenous treatment of SCD neutrophils with RvD1 and D4 significantly dampened NETs release and enhanced NETs clearance by macrophages. RvD4 along with other pro-resolving mediators also stimulated ex vivo clearance of P. aeruginosa and S. aureus by SCD neutrophils. Our findings provide a novel link between autoimmunity and neutrophil-mediated vasculopathy in SCD and highlight the importance of Rv and their immune-pro-resolution effects in limiting disease progression in SCD but also to modulate the host response to infections and sepsis, which is altered in SCD.

Acute Hypokalemic Paralysis Secondary to Distal Renal Tubular Acidosis Presenting as Guillain Barre Syndrome

A 52 year old female patient presented to emergency casualty with Acute onset quadriparesis with respiratory muscle involvement in. During initial work up Serum electrolytes showed severe hypokalemia. Arterial blood gas showed normal anionic gap metabolic acidosis with positive urine anion gap and urine examination showed alkaline PH in the presence of systemic acidosis. All these findings suggest Distal Tubular Acidosis. Further evaluation revealed strongly positive Anti nuclear antibodies with SS-A also being positive suggesting Sjogren’s Syndrome.

HBH DISEASE AND SYSTEMIC LUPUS ERYTHEMATOSUS

The association between thalassemia and systemic lupus erythematosus (SLE) is very rare. There are many articles in the literature showing that patients diagnosed with SLE with Beta-Thalassemia have a more severe hemolytic picture. The combination of Alpha thalassemia and SLE was first reported in an article published on January 30, 2021, by the staff of Guangzhou Hospital in the People's Republic of China. Our report is about combination of HbH disease and SLE, too. A 31-year-old female patient with HbH disease who had been irregularly monitored by a hematologist for 12 years received a blood transfusion for the first time during her 4th pregnancy and has not seen a hematologist since. At 12 weeks of gestation (7th pregnancy), a severe hemolytic anemic clinic was observed and erythrocyte mass transfusion was initiated. However, as different types of allergic reactions were observed during and after hemotransfusions autoimmune tests were held. As a result, Direct Antiglobulin Test (DAT), Anti Nuclear Antibody (ANA), and anti-dsDNA positive, complement C3 levels were found below standard. The diagnosis of SLE was confirmed based on the fact that the patient's previous 6 pregnancies resulted in miscarriages and stillbirth. At a later stage, as a result of detailed instrumental and laboratory examinations, she was diagnosed with Lupus nephritis and steroid treatment was started under the control of a nephrologist. Unit erythrocyte mass was transfusioned during cholecystectomy in this patient who was taken to the hospital with seizure pain in the right subcostal area that suddenly began at 22 weeks of gestation. 24-week pregnancy was ceased due to intrauterine growth retardation. In the next month of follow-up, during the hospitalization 7 units of washed erythrocyte mass were transfused to the patient who was brought to the hospital with severe anemia after positive Covid-19 PCR analysis. In case published about the first patient with HbH disease and SLE it was reported an increase in the severity of anemia and the maintenance of Hb value in the range of 9.0-10.0 g / dl with steroid. According to our researchs there were found similarities between the outcomes of these two studies. Studies suggest that SLE patients with severe hemolytic clinics in regions with a high prevelance of thalassemia should be investigated for hemoglobinopathies.

Osteonecrosis of the Jaw Caused by Denosumab in Treatment-Naïve and Pre-Treatment with Zoledronic Acid Groups: A Time-to-Onset Study Using the Japanese Adverse Drug Event Report (JADER) Database.

Medication-related osteonecrosis of the jaw is a serious adverse event associated with bone-modifying agents, such as injectable bisphosphonate (zoledronic acid) and the anti-receptor activator of nuclear factor-κB ligand antibody (denosumab). This study aims to evaluate and compare the time-to-onset profile for medication-related osteonecrosis of the jaw associated with denosumab between treatment-naïve (naïve group) and pre-treatment with zoledronic acid (post-zoledronic acid group) patients using the Japanese Adverse Drug Event Report database. Medication-related osteonecrosis of the jaw was defined according to the Medical Dictionary for Regulatory Activities. The medication-related osteonecrosis of the jaw onset profiles were evaluated using the Weibull shape parameter and the log-rank test. The Japanese Adverse Drug Event Report database contains 632,409 reports published between April 2004 and March 2020. In the time-to-onset analysis, after extracting the combinations with complete information for the treatment start date and the medication-related osteonecrosis of the jaw onset date, 272 reports of the naïve group and 86 reports of the post-zoledronic acid group were analyzed. The median onset in the naïve and post-zoledronic acid groups was 487.0 (25-75%: 274.0-690.8) and 305.5 (25-75%: 158.3-508.5) days, respectively. Medication-related osteonecrosis of the jaw occurred earlier in the post-zoledronic acid group than in the naïve group, and the log-rank test demonstrated a significant difference in their time transitions (p < 0.0001). The results indicated a risk of medication-related osteonecrosis of the jaw in naïve and post-zoledronic acid groups and a shorter onset time in the latter than in the former. Thus, healthcare professionals should take the early risk of medication-related osteonecrosis of the jaw into account when switching patients from zoledronic acid to denosumab treatment.

Renal Transplantation in Pure Autonomic Failure.

Renal Transplantation in Pure Autonomic Failure.

Microgravity-Related Changes in Bone Density and Treatment Options: A Systematic Review.

Space travelers are exposed to microgravity (µg), which induces enhanced bone loss compared to the age-related bone loss on Earth. Microgravity promotes an increased bone turnover, and this obstructs space exploration. This bone loss can be slowed down by exercise on treadmills or resistive apparatus. The objective of this systematic review is to provide a current overview of the state of the art of the field of bone loss in space and possible treatment options thereof. A total of 482 unique studies were searched through PubMed and Scopus, and 37 studies met the eligibility criteria. The studies showed that, despite increased bone formation during µg, the increase in bone resorption was greater. Different types of exercise and pharmacological treatments with bisphosphonates, RANKL antibody (receptor activator of nuclear factor κβ ligand antibody), proteasome inhibitor, pan-caspase inhibitor, and interleukin-6 monoclonal antibody decrease bone resorption and promote bone formation. Additionally, recombinant irisin, cell-free fat extract, cyclic mechanical stretch-treated bone mesenchymal stem cell-derived exosomes, and strontium-containing hydroxyapatite nanoparticles also show some positive effects on bone loss.

THE POTENTIAL ROLE OF EPSTEIN-BARR VIRUS NUCLEAR ANTIGEN-1 (EBNA-1) IN MULTIPLE SCLEROSIS

Background: Multiple sclerosis (MS) is a disease affecting the central nervous system (CNS), with inflammation and demyelination of nerves, eventually resulting in nerve damage and disabilities. The risk of developing MS enlarged by infectious mononucleosis, which is caused by delayed primary infection by Epstein-Barr Virus (EBV). Early reports consistently demonstrated an increased antibody response in MS patients versus healthy subjects towards different EBV antigens, including the EBV nuclear antigen-1 (EBNA-1). In Iraq, number of researchers found that the EBV have a possible role at some point in the course of the disease, others reported that the EBV pathogenesis have an important role in the triggering of MS disease. Objective: To compare the sero-prevalence of EBV nuclear antigen-1 antibody (EBNA-1 IgG) among the Iraqi MS patients and controls and find out whether there is a relation between disease severity and EBNA-1 IgG titer. Methods: This case-control study conducted on 120 MS patients aged between 13-42 years, and 120 apparently healthy age- and sex-matched volunteers as controls. Three ml of whole blood were collected from all MS patients and controls and put in gel tubes. The blood samples were centrifuged at 5000 RPM for 5 minutes to get serum from the gel tubes. Serum was preserved in (-20ºC), and then used for enzyme-linked immunosorbent assay (ELISA). The ELISA study was performed using ELISAs kits (Abnova /Taiwan) for EBNA-1 IgG antibodies measurement. Results: EBNA-1 IgG was positive in 51.7% (62/120) of MS patients and 39.2% (47/120) of controls, (P=0.035). The median of EBNA-1 IgG level of MS patients and controls were 81.08 U/ml, and 67.73 U/ml, respectively (P=0.043). And EBNA-1IgG was significantly higher in younger age groups. Patients with the first-line and second-line treatment showed no significant differences in EBNA-1 IgG levels, while the median level in patients without treatment (newly diagnosed) and those who were at early years of the disease was higher. Conclusion: EBNA-1 antibody could play a triggering role in MS because it is significantly higher in MS patients than in controls, especially at younger age groups, early stages of the disease and in female patients. Keywords: Multiple sclerosis, EBV, EBNA-1 IgG, ELISA Citation: Ali ZA, Al-Obaidi AB, Almashta SA. The potential role of Epstein-Barr Virus Nuclear Antigen-1 (EBNA-1) in multiple sclerosis. Iraqi JMS. 2022; 20(1): 3-10. doi: 10.22578/IJMS.20.1.2

P1646: PRIMARY IMMUNE THROMBOCYTOPENIA (ITP) IN PATIENTS OLDER THAN 75 YEARS: REAL WORLD DATA FROM THE ITP REGISTRY OF THE HELLENIC SOCIETY OF HEMATOLOGY

Background: ITP incidence is known to increase in adults aged >60 years and even more in men aged >75 years (Moulis G et al., Blood 2014; 124(22):3308). As population aging and life-expectancy continues to increase worldwide, ITP in the elderly is a growing concern in everyday clinical practice. There are only a few studies regarding the features of ITP in patients (pts) aged >60-65 years and data are even scarcer in pts aged ≥75 years Aims: To describe real world characteristics at diagnosis and evaluate disease outcome in a group of pts aged 60-74 years (Group-1) as compared to very old pts (≥75 years; Group-2) with primary ITP, using data from the national database (ITP registry) operated under the auspices of the Hellenic Society of Hematology Methods: The Greek ITP registry recruits pts (n=1560, to date) nationally through a network of 25 sites. In the present study we retrospectively analyzed data from pts with primary ITP aged ≥60 years, who were diagnosed from 1979 to 2021. Results: The total number of evaluable pts was 298. Group-1 consisted of 180 and Group-2 of 118 pts. The mean age at diagnosis was 68 years (60.1-74.9) in Group-1 and 81 years (75.2-97.1) in Group-2. The female to male ratio did not differ between the 2 groups. The median platelet count at diagnosis was significantly higher in Group-1 (20x109/L, interquartile range: 5-44x109/L) than in Group-2 (11x109/L, interquartile range: 5-32x109/L; P=0.0096). Comorbidity rates did not differ between Group-1 and Group-2, with the exception of hypertension and chronic kidney disease, which were less frequently reported in Group-1 (P=0.0092 and P=0.0179, respectively). Concurrently used medications as a whole and also vitamin-K antagonists were reported less frequently in Group-1 (P=0.03 and P=0.049, respectively). Bleeding manifestations at diagnosis were comparable across the two age-groups. The choice of diagnostic procedure did not differ between Goup-1 and Group-2, with the exception of anti phospholipid antibody and anti nuclear antibody testing which were performed more frequently in Group-1 (P=0.048 and P=0.0002, respectively). Similar rates of positive laboratory test results were reported in the two age-groups. Fewer pts received treatment at diagnosis in Group-1 (P=0.023). Overall response rate did not differ between the two Groups. A similar proportion of Group-1 and Group-2 patients were treated with corticosteroids, intravenous IgG or both, rituximab, anti-D, immunoglobulin or thrombopoietin receptor agonists. Splenectomy was performed in 2.8% of Group-1 pts but in none of Group-2 pts. At 1 year after diagnosis, a similar proportion of Group-1 and Group-2 pts had developed chronic ITP. Summary/Conclusion: Very elderly pts (Group-2) presented with lower platelet counts at diagnosis and required ITP treatment more frequently than elderly pts (Group-1). Furthermore, Group-2 pts suffered more often from hypertension and chronic kidney disease and used more often anticoagulant agents. On the other hand, the 2 age-groups did not differ in the frequency or the location of bleeding. Age did not seem to particularly influence the diagnostic workup or the choice of treatment, with the exception of splenectomy which was not performed in Group-2 patients. The outcome of the disease was comparable in the 2 age-groups, as suggested by the similar treatment response rates and chronic ITP frequencies. Further investigation is warranted to full characterize the very elderly pts with ITP and unravel the unmet need of this cohort in order to optimize management.

Antibody response to herpes simplex virus-1 is increased in autoimmune encephalitis.

Antibody response to herpes simplex virus-1 is increased in autoimmune encephalitis.

Clinical implications of autoantibodies to extractable nuclear antigens in rheumatoid arthritis patients in tertiary care hospital in Riyadh, Saudi Arabia

The purpose of this study was to assess the prevalence of autoantibodies against extractable nuclear antigens (ENAs), anti-Ro/SSA, anti La/SSB, anti Jo-1, ribo-nucleoproteins (anti UI-RNP) and antibodies to Smith (anti-Sm) in rheumatoid arthritis (RA) patients and to detect the relationship between the existence of these autoantibodies and clinical presentation, radiological damage, and disease activity markers. The study, included 57 RA patients and 35 normal controls, was conducted in Al-Quwayiya General Hospital. Sera were obtained from patients and controls to carry out Hs-CRP, ESR, RF factors, ANA and ACPA IgG. Anti-Sm, anti-U1-RNP, anti-Ro/SSA, anti-La/SSB, and anti-Jo-1 were measured using the Alegria® assay. ESR was 23.8±6.5, while CRP was 16.19±7.15 in RA patients. RF was detected in 23 (40.35%) patients and ACPA in 54 (94.73%), while ANA was positive in 14 (24.56%) cases. Anti-Ro/SSA was detected in 8 (14.03%) patients, anti-La/SSB in 3 (5.26%), anti-Jo-1 was found in 2 cases (3.50%), and anti-RNP in 1 (1.75%). Anti-Ro/SSA had a significant negative relationship with sex (r=-0.220, P=0.001), but a positive correlation was observed with sicca symptoms (r=0.149, P=0.02). Anti-La/SSB antibodies correlated positively with swollen joint count (r=0. 0.225, P=0.001), tender joint count (r=0.219, P=0.001) and ANA (r=0.367, P < 0.001). Anti-Jo-1 antibodies showed a significant positive correlation with interstitial lung disease (r=-0.429, P≤0.001). Anti-Ro/SSA had a significant positive correlation with RF titer (r=0.259, P < 0.001) and ANA (r=0.498, P < 0.001). Anti-La/SSB had significant positive correlation with ANA (r=0.372, P < 0.001). Anti-Jo-1 showed a significant positive correlation with RF titer (r=0.141, P < 0.040) and ANA (r=0.249, P < 0.001). Anti-RNP showed a significant positive correlation with ACPA titre (r=0.288, P < 0.001) and ANA (r=0.159, P < 0.018). We conclude that ENA autoantibodies are crucial and need to be correlated with clinical diagnosis and other serological testing for early diagnosis and intervention of the RA.

A Study of the Standardization and the External Quality Assessment for Antinuclear Antibody, Anti-Double-Stranded DNA, and Anti-Extractable Nuclear Antigen Antibody Testing

A Study of the Standardization and the External Quality Assessment for Antinuclear Antibody, Anti-Double-Stranded DNA, and Anti-Extractable Nuclear Antigen Antibody Testing

Low Prevalence of Anti-DFS70 Antibodies in Children With ANA-Associated Autoimmune Disease.

IntroductionAnti-DFS70 antibodies occur in healthy individuals with various medical conditions. Unlike other anti-nuclear autoantibodies (ANA), they are not associated with systemic autoimmune disease in adult patients. To date, only a few studies have addressed the prevalence and/or clinical relevance of anti-DFS70 autoantibodies in children with and without autoimmune disease.MethodsIncluded in this retrospective cross-sectional mono-centric study were 308 pediatric patients with suspected or known autoimmune conditions who had a positive ANA in indirect immune fluorescence (IIF) screening and who were screened for anti-DFS70 antibodies by extractable nuclear antigen antibodies (ENA) immunoblot. Patients were assigned to four different diagnostic categories according to their diagnosis in the corresponding medical record: (a) absence of autoimmune or rheumatic disease (noARD, n = 116); (b) suspected autoimmunity without definitive diagnosis (sAI, n = 48); (c) other rheumatic disease (ORD) (n = 115); and (d) ANA-associated autoimmune disease (AARD, n = 29).ResultsThe prevalence of anti-DFS70 antibodies in the overall cohort was 33.8%. Among children without ARD (46.6%, 54/116), prevalence was significantly higher than among children with ORD (23.7%, 27/115, p = 0.0003) or AARD (17.2%, 5/29, p = 0.0054). Among all of the anti-DFS70 positive patients with AARD, other autoantibodies were found in the ENA immunoblot. In contrast, among anti-DFS70 positive patients with ORD (11.5%, 4/27), sAI (33.3%, 6/18) and noARD (16.7%, 9/54), other autoantibodies infrequently were detected (p = 0.0005). Patients with uveitis rarely were positive for anti-DFS70 antibodies (7.7%, 1/13). No association was found between anti-DFS70 antibodies and a history of allergic conditions (p = 0.51). The concordance between a typical DFS pattern in IIF and the detection of anti-DFS70 antibodies by immunoblot was 59.3%.ConclusionAs with adults, the higher prevalence of anti-DFS70 among children without autoimmune disease confirms the mutual exclusion for this autoantibody in the pathogenesis of ARD. Among ANA-positive children, monospecific anti-DFS70 antibodies may help to discriminate between AARD and not-AARD-related conditions.

Autoimmune and Paraneoplastic Chorea: A Review of the Literature.

Autoimmune chorea syndromes represent a vast array of paraneoplastic, parainfectious and idiopathic disorders. It is increasingly apparent that familiarity with these disorders is critically important, as they may be treatable or may be part of a syndrome requiring further work-up and monitoring. These disorders are mediated by an aberrant immunologic attack with resultant neuronal dysfunction, manifesting as chorea. These conditions are typically accompanied by other neurologic or systemic manifestations. In this review we outline the clinical features, epidemiologic factors, and delineate the specific antibodies associated with each of these autoimmune mediated disorders. We highlight up to date information regarding this heterogeneous group of disorders, including a discussion of parainfectious Sydenham's chorea; paraneoplastic syndromes associated with CRMP-5 (collapsin response mediated protein-5/CV2) and ANNA-1 (antineuronal nuclear antibody / Hu) antibodies, in addition to neuronal antibody-associated disorders including anti-NMDAR, LGI1 (leucine-rich glioma inactivated-1) and CASPR2 (contactin associated protein-2). We discuss the more recently described entities of IgLON5, which has evidence of both immunologic and degenerative pathophysiology, in addition to PDE-10A antibody-associated chorea. We also outline chorea secondary to systemic diseases including Systemic Lupus Erythematosus (SLE) and Primary Antiphospholipid Syndrome (PAPS). We provide a framework for diagnosis and treatment.

Drug treatment algorithm and recommendations from the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publication.

The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA; JCR CPG for RA) according to recent changes in the medical environment in Japan. This article is a digest version of the guidance. We used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. A consensus was formed by CPG panel members. We identified 36 important clinical questions regarding drug treatment and developed corresponding recommendations for RA. The recommendations included the following RA medications: non-steroidal anti-inflammatory drugs, corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, biological disease-modifying antirheumatic drugs, anti-receptor activator for nuclear factor-κB ligand antibodies, and Janus kinase inhibitors, as well as the tapering and discontinuation of these medications. Recommendations regarding the efficacy and safety of treatments in the elderly and patients with comorbidities were also developed. Finally, we used these recommendations to create an original algorithm for drug treatment for RA based on the Treat-to-Target approach. The 2020 JCR CPG for RA provides a useful tool for rheumatologists, health care professionals, and patients with RA, enabling shared decision-making in a variety of clinical situations.

Spontaneous regression of breast lymphoproliferative disorders after withdrawal of methotrexate in rheumatoid arthritis patients with Epstein\u2013Barr virus infection: a case report and review of the\xa0literature

BackgroundLymphoproliferative disorder (LPD) has been shown to occur after treatment with methotrexate (MTX). Currently, MTX-LPD has become widely recognized, but its mechanism and prognostic factors remain unclear.Case presentationWe report the first case of Epstein–Barr virus (EBV)-associated MTX-LPD of the breast. A 63-year-old Asian woman with long-term rheumatoid arthritis presented to our facility with intermittent fever. A physical examination revealed a 3-cm lump in her left breast. She had been taking MTX for the past 15 years. Laboratory studies revealed slightly elevated levels of EBV-viral capsid antigen antibody immunoglobulin G and EBV nuclear antibody. Contrast-enhanced computer tomography revealed a mass in the left breast, a subcutaneous nodule in the abdomen, a mass in the left lung, and a nodule in the left retroperitoneum. The definitive diagnosis was consistent with MTX-LPD merging into an EBV-positive, diffuse large B-cell lymphoma. Six months following the withdrawal of MTX, the breast mass had markedly shrunk and the patient remained in good health for 1 year with no evidence of relapse of LPD.ConclusionMTX-LPD rarely occurs in the breast, and it is difficult to diagnose because there have only been six reported cases of breast MTX-LPD reported in the literature. EBV-positive MTX-LPD tends to regress spontaneously after MTX withdrawal, and our case also had similar results. It is important to make an appropriate diagnosis of MTX-LPD of the breast based on imaging and pathology to determine the appropriate treatment protocol for this rare disorder.