Presence Of Autoantibodies Research Articles

Rare case of acquired hemophilia B with positive lupus anticoagulant: presenting with bleeding and thrombosis

Objectives. We present an exceptionally rare case of acquired hemophilia B coexisting with lupus anticoagulant (LA), with the concurrent presentation of bleeding and thrombosis. This unique and challenging case poses significant diagnostic and management difficulties for clinicians. Case presentation. A 45-year-old male presented with severe cephalgia, gastrointestinal bleeding, and a subacute subdural hematoma. Laboratory investigations revealed prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), positive LA, and a significant reduction in factor IX levels. Despite receiving fresh frozen plasma (FFP) and packed red cells (PRC), the patient’s coagulation abnormalities persisted. Outcome. Further investigation led to the diagnosis of acquired hemophilia B with positive lupus anticoagulant. We suspected that a factor inhibitor or vitamin K deficiency might be contributing to the bleeding disorder, necessitating additional confirmatory diagnostics. The patient ultimately chose to be discharged against medical advice, highlighting the ongoing challenges in diagnosing and managing such complex conditions. Conclusions. Bleeding disorders in the presence of autoantibodies require comprehensive diagnostic testing, including specific factor inhibitor assays, to guide appropriate treatment. The coexistence of both bleeding and thrombosis in this patient illustrates the paradoxical effects of LA on coagulation, providing valuable insights for clinicians encountering similar cases.

Decoding Dystonia in Autoimmune Disorders: A Scoping Review.

Dystonia is a common hyperkinetic movement disorder observed in various genetic, infective, drug-induced, and autoimmune disorders. Autoimmune disorders can present with isolated or combined acute or subacute dystonia. The pattern and approach to dystonia in autoimmune disorders are poorly described and have never been established in a structured manner. This scoping review aims to summarize all available clinical literature and formulate a pattern and approach to dystonia in different autoimmune disorders. We included one hundred and three articles in this scoping review. Most articles identified were case reports or case series. In this review, we analysed data from 103 articles and summarized the epidemiological, clinical, and diagnostic features of dystonia associated with different autoimmune diseases. We highlight that dystonia can be isolated or combined in various autoimmune conditions and is responsive to immunotherapy. We point out the patterns of dystonia and associated neurological features and investigations that can suggest the underlying autoimmune nature, which can guide the most appropriate treatment. The clinical pattern of dystonia can be a unique feature in many autoimmune disorders. In isolated subacute dystonia, the presence of autoantibodies could have a temporal association, or this is just an epiphenomenon to be evaluated in further research. Many autoimmune disorders can present with isolated or combined dystonia.Subacute onset focal or segmental dystonia (craniocervical dystonia or limb dystonia) or hemidystonia could be secondary to an autoimmune condition and warrants investigations.They have a relapsing or progressive course.They usually have a good response to early immunotherapy.Symptomatic treatment, including botulinum toxin, can be useful in focal dystonia.

The Potential Role of Neutrophil Reactivity Intensity and Reactive Lymphocytes as Extended Hematological Parameters to Detect Active Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of autoantibodies against nuclear antigens and immune complex deposition. The pathogenesis of SLE is not fully understood; however, there are alterations in neutrophils and lymphocytes. Recent parameters assessing both neutrophil activations (Neut-RI, Neut-GI, IG) and activated lymphocytes (Re-Lymp, As-Lymp) can be used to assess the activation of immune cells. The aim of this study was to explore the potential role of this parameter in detecting active SLE. Cross-sectional study using secondary data from Hasan Sadikin Lupus Registry. Parameters were examined using Sysmex XN-1500. Lupus activity was determined according to SLEDAI-2K. This study included 30 active (SLEDAI 2K ≥ 4) and 30 inactive SLE patients. Compared to inactive SLE, active SLE showed significantly higher Neut-RI (51.5 vs. 49.6 FL, p = 0.004), and lower Re-Lymph (0.09 vs. 0.14 × 103/mm3, p = 0.024). There was no significant difference in Neut-GI (150 vs. 151.6 SI, p = 0.359), As-Lymp (0.02 vs. 0.01 × 103/mm3, p = 0.621), and IG (0.11 vs. 0.06 × 103/mm3, p = 0.384) between active and inactive SLE. Neut-RI/Re-Lymp ratio cutoff > 0.47 could distinguish between active and inactive SLE with AUC 0.689, 66.7% sensitivity, and 70.0% specificity. In active SLE, there is an elevation in Neut-RI and a reduction in Re-Lymp. Neut-RI/Re-Lymp ratio exceeding 0.47 could be used to detect active SLE.

De Novo C3 Glomerulonephritis of Allograft Associated with Factor H Autoantibody in a Patient with Systemic Lupus Erythematosus: A Case Report

C3 Glomerulonephritis (C3GN) is a rare disease with a challenging diagnosis and poor prognosis. It is characterized by dysregulation of alternate complement pathway and diagnosed by biopsy findings of isolated or predominant C3 deposits on immunofluorescence (IF) staining. Dysregulation of alternate complement pathway (ACP) caused by genetic mutations or autoantibodies leads to C3 glomerulopathy (C3G) and complement-mediated thrombotic microangiopathies (c-TMA), later also referred to as atypical hemolytic uremic syndrome (aHUS). Autoantibodies like C3 nephritic factor and Factor H autoantibodies (FHAA) are frequently seen as acquired abnormalities in C3GN. SLE is a multi-system complex disorder distinguished by the presence of autoantibodies to multiple nuclear antigens, including DNA and ribonucleoprotein leading to complement activation, characterized by low level of C3 and C4 and may present with c-TMA. There are not many cases of C3GN with SLE that have been described, and current literature lacks strong evidence-based treatment options of post-transplant C3GN. Here, we describe a case of de novo C3GN of allograft in a patient with SLE.

Dermatological complications due to post‑COVID‑19 syndrome: A systematic review.

Almost 20% of patients affected by COVID-19 develop dermatological symptoms after recovery. This condition is termed as post-COVID-19 syndrome and is characterized by a state of hyperinflammation, as well as deregulations in the humoral response of CD8+ T-cells. Since there is no specific treatment for these injuries, the treatment of choice depends on the symptoms; thus, it is essential to provide a description of the type and nature of the injuries presented. In the present study, a systemic review was performed using the PICO strategy in the repositories of PubMed, Google Scholar, Embase and Scopus using the key words 'POST-COVID and skin symptoms'. A total of 44 studies were included in the present systematic review. In these studies, the majority of subjects exhibited non-specific symptoms, commonly referred to as 'skin rash', affecting up to 27.4% of the population. According to the studies, a maximum prevalence of 50% of alopecia was observed among the affected subjects. Additionally, several studies reported the prevalence of other lesions, including pruritus (25%), subcutaneous nodules (12%), dermatitis (9.4%), edema (9%) and pigmentation changes (6%). Dermatological lesions associated with autoimmunity were also identified, with these findings being more pronounced among females and in patients with a history of severe COVID-19. Finally, several studies investigated the presence of autoantibodies, revealing a maximum prevalence of 41% for autoantibodies targeting the epidermis. Specifically, the prevalence was 12.9% for the Wuhan variant, 5.7% for the Alpha variant and 5% for the Delta variant. Although mostly benign, post-COVID-19 syndrome produces marked dermatological alterations for hair health, mainly among females. This, together with the development of lesions with an autoimmune component, constitutes an emerging therapeutic need.

Detailed Pathophysiology of Minimal Change Disease: Insights into Podocyte Dysfunction, Immune Dysregulation, and Genetic Susceptibility.

Minimal Change Disease (MCD) is a predominant cause of idiopathic nephrotic syndrome in the pediatric population, yet presents significant clinical challenges due to its frequent relapses and steroid resistance. Despite its relatively benign histological appearance, MCD is characterized by severe proteinuria, hypoalbuminemia, and edema, which may affect patient outcomes. Current treatment strategies primarily rely on corticosteroids, which are effective in inducing remission but are associated with high relapse rates, steroid resistance, and numerous long-term side effects, underscoring the need for more targeted and effective therapeutic approaches. This narrative review synthesizes current knowledge on the pathophysiological mechanisms underlying MCD, focusing on the following three critical areas: podocyte dysfunction, immune dysregulation, and genetic susceptibility. Podocyte dysfunction, particularly involving alterations in nephrin, plays a central role in the breakdown of the glomerular filtration barrier, leading to the characteristic proteinuria observed in MCD. Immune dysregulation, including the presence of autoantibodies against nephrin and other podocyte components, exacerbates podocyte injury and contributes to disease progression, suggesting an autoimmune component to the disease. Genetic factors, particularly mutations in the NPHS1 and NPHS2 genes, have been identified as significant contributors to disease susceptibility, influencing the variability in treatment response and overall disease severity. Understanding these mechanisms is crucial for developing targeted therapies that address the underlying causes of MCD rather than merely managing its symptoms. This review highlights the need for further research into these pathophysiological processes to pave the way for more personalized and effective treatment strategies, ultimately improving patient outcomes and reducing reliance on corticosteroids.

Unusual Association: Dermatomyositis Diagnosis Tied to Rare Presence of TPO Autoantibodies

The co-occurrence of autoimmune diseases is prevalent and largely documented. However, the simultaneous presence of dermatomyositis and autoimmune thyroid disorders remains comparably uncommon, despite both being autoimmune in nature. In this report, we present a case of a 60-year-old Bangladeshi American individual delineating clinical manifestations consistent with dermatomyositis, including Gottron's papules, the V-sign, Shawl sign, and skin abnormalities, noticeably hypopigmented areas on the scalp and face. Although muscle biopsy results in this patient did not align strictly with classical dermatomyositis, they illustrated a combination of necrotizing myopathy and dermatomyositis. Notably, laboratory findings conceded the presence of TPO autoantibodies, despite the absence of clinical signs or symptoms of hypothyroidism. This discovery recommends the possibility of an underlying autoimmune thyroid condition. Our case prompts consideration of whether a distinct subtype of dermatomyositis may be associated with autoimmune thyroid conditions, even in the absence of overt thyroid manifestations.

Looking back at the TEDDY study: lessons and future directions.

The goal of theTEDDY (The Environmental Determinants of Diabetes in the Young) study is to elucidate factors leading to the initiation of islet autoimmunity (first primary outcome) and those related to progression to type 1 diabetes mellitus (T1DM; second primary outcome). This Review outlines the key findings so far, particularly related to the first primary outcome. The background, history and organization of the study are discussed. Recruitment and follow-up (from age 4 months to 15 years) of 8,667 children showed high retention and compliance. End points of the presence of autoantibodies against insulin, GAD65, IA-2 and ZnT8 revealed the HLA-associated early appearance of insulin autoantibodies (1-3 years of age) and the later appearance of GAD65 autoantibodies. Competing autoantibodies against tissue transglutaminase (marking coeliac disease autoimmunity) also appeared early (2-4 years). Genetic and environmental factors, including enterovirus infection and gastroenteritis, support mechanistic differences underlying one phenotype of autoimmunity against insulin and another against GAD65. Infant growth and both probiotics and high protein intake affect the two phenotypes differently, as do serious life events during pregnancy. As the end of the TEDDY sampling phase is approaching, major omics approaches are in progress to further dissect the mechanisms that might explain the two possible endotypes of T1DM.

Simultaneous Pancreas-Kidney Transplant Outcomes Stratified by Autoantibodies Status and Pretransplant Fasting C-peptide.

Pancreatic beta cell function and islet autoantibodies classically distinguish types of diabetes (type 1 diabetes mellitus [DM] or type 2 DM). Here, we sought to evaluate simultaneous pancreas-kidney (SPK) transplant outcomes stratified by the presence or absence of beta cell function and autoantibodies. SPK recipients were eligible if pretransplant autoantibodies were measured against insulin, islet cell, or glutamic acid decarboxylase 65-kD isoform. Recipients were categorized as A+ or A- based on the detection of ≥1 autoantibodies. Recipients were similarly categorized on the basis of detectable pretransplant fasting C-peptide of ≥2 ng/mL (β+) or <2 ng/mL (β-). Thus, recipients were categorized into 4 groups: A+β-, A-β-, A-β+, and A+β+. Outcomes of interest were overall pancreas graft failure (non-death-censored), death-censored pancreas, or kidney graft failure (death-censored pancreas graft failure [DCGF]; kidney DCGF), composite outcomes with any of the 3 outcomes as pancreas DCGF, use of an antidiabetic agent, or hemoglobin A1c >6.5. One hundred eighty-three SPK recipients were included: A+β- (n = 72), A-β- (n = 42), A-β+ (n = 49), and A+β+ (n = 20). We did not detect a statistical difference in non-death-censored pancreas graft failure for A+β- recipients compared with other groups: A-β- (adjusted hazard ratio [aHR]: 0.44; 95% confidence interval [CI], 0.14-1.42), A-β+ (aHR: 1.02; 95% CI, 0.37-2.85), and A+β+ (aHR: 0.67; 95% CI, 0.13-3.33) in adjusted analyses. Similar outcomes were observed for other outcomes. In SPK recipients, outcomes were similar among recipients with classic features of type 1 DM and various other types of DM.

Novel autoantibody targets identified in patients with autoimmune hepatitis (AIH) by PhIP-Seq reveals pathogenic insights.

Autoimmune hepatitis (AIH) is a severe disease characterized by elevated immunoglobin levels. However, the role of autoantibodies in the pathophysiology of AIH remains uncertain. Phage Immunoprecipitation-Sequencing (PhIP-seq) was employed to identify autoantibodies in the serum of patients with AIH (n = 115), compared to patients with other liver diseases (metabolic associated steatotic liver disease (MASH) n = 178, primary biliary cholangitis (PBC), n = 26, or healthy controls, n = 94). Logistic regression using PhIP-seq enriched peptides as inputs yielded a classification AUC of 0.81, indicating the presence of a predictive humoral immune signature for AIH. Embedded within this signature were disease relevant targets, including SLA/LP, the target of a well-recognized autoantibody in AIH, disco interacting protein 2 homolog A (DIP2A), and the relaxin family peptide receptor 1 (RXFP1). The autoreactive fragment of DIP2A was a 9-amino acid stretch nearly identical to the U27 protein of human herpes virus 6 (HHV-6). Fine mapping of this epitope suggests the HHV-6 U27 sequence is preferentially enriched relative to the corresponding DIP2A sequence. Antibodies against RXFP1, a receptor involved in anti-fibrotic signaling, were also highly specific to AIH. The enriched peptides are within a motif adjacent to the receptor binding domain, required for signaling and serum from AIH patients positive for anti-RFXP1 antibody was able to significantly inhibit relaxin-2 singling. Depletion of IgG from anti-RXFP1 positive serum abrogated this effect. These data provide evidence for a novel serological profile in AIH, including a possible functional role for anti-RXFP1, and antibodies that cross react with HHV6 U27 protein.

The role of angiotensin II and endothelin receptor antibodies in COVID19 patients with HFpEF

Abstract Background The infection caused by the coronavirus SARS-COV-2, is associated with an unusual pattern of organ damage in comparison to other viral-induced pathologies. A theory of autoimmunity induced by ACE-2/SARS-COV-2 spike protein complex or its degradation products, was proposed as a possible explanation for the versatile and multiorgan damage in COVID-19. Aim The aim of the study is to determine whether antibodies against angiotensin II receptor type 1 (AT1R) or endothelin-1 receptor type A (ETAR) do exist in plasma of COVID -19 patients with heart failure with preserved ejection fraction and whether they correlate to the severity of the disease. Methods A total of 61 patients with COVID-19 and heart failure with preserved ejection fraction and 48 controls (free of COVID19) with heart failure with preserved ejection fraction were included. Patients were divided into two groups: patients with severe disease (admitted at the intensive care (n=30)), patients with milder clinical presentation that remained in the general therapeutical department (n=31). The plasma levels of IL-6 and auto-antibodies against AT1R or ETAR in peripheral blood were measured and compared between COVID19 patients with severe and milder disease and age matched controls. Clinical and standard laboratory parameters were also collected and their association with the research biomarkers was analysed. Results Auto-antibodies against AT1R were significantly increased in severe disease course (median 19.60 U/mL, IQR 4.8-34.75) compared to milder disease (median 10.95 U/mL, IQR 7.69 – 17.67, p=0.017) and the control group (median 6.79 U/mL, IQR 5.10 – 14.05, p&amp;lt; 0.001). ETAR antibody titers were also significantly increased in severe disease (median 14.52, IQR 6.76-32.94), compared to milder disease course (median 8.73 U/mL, IQR 6.59 –13.45, p=0.023) and to the control group (median 6.64, IQR 6.79 – 17.92, p &amp;lt;0.001). The same was the trend regarding IL-6 antibodies. Severe disease (median 12.11 U/mL, IQR 5.59–19.38); milder disease disease (median 8.64U/mL, IQR 1.84 – 14.13, p=0.039); control group (median 4.28U/mL, IQR 0.11–1.43, p&amp;lt;0.001).Both AT1R and ETAR correlated to IL-6 plasma levels. The results did not show association with the concomitant therapy. Conclusion In conclusion, we establishеd the presence of AT1R and ETAR autoantibodies in COVID-19 patients with heart failure with preserved ejection fraction. They correlated to IL-6 plasma levels (systemic inflammation) and are associated with severe form of the disease.

Increased risk of stroke in non-rheumatic valvular disease associated with antiphospholipid syndrome (APS): a US nationwide study 2017-2019

Abstract Introduction Antiphospholipid syndrome (APS) is an autoimmune syndrome characterized by the presence of antiphospholipid autoantibodies, arterial and venous thrombosis, recurrent pregnancy loss and thrombocytopenia. Cardiac manifestations are also common which include coronary artery disease (CAD), non rheumatic valvular heart disorders (NRVHD), myocardial dysfunction, intracardiac thrombi and pulmonary hypertension. Valvular lesions occur likely due to immune complex deposition on the valves, causing fibrosis, calcification and subsequently valvular deformities. Literature review suggests prevalence of NRVHD in APS population is 30% and left sided valves are more involved than right. An increased risk of stroke has also been seen in APS patients with valvular disorders. Purpose Studies report variations in incidence of NRVHD in association with APS. To estimate the prevalence of NRVHD and their correlation with APS, we conducted a retrospective database analysis of hospitalizations across the United States. Additionally we investigated whether this association indicates a increased risk of ischemic stroke in this specific subpopulation. Methods The national inpatient sample (NIS) from 2017-2019 was queried for adult patients (age&amp;gt;18 yrs) admitted with a primary or secondary diagnosis of APS. These patients were stratified for different NRVHD including tricuspid stenosis, tricuspid insufficiency, pulmonary stenosis, pulmonary regurgitation, mitral stenosis, mitral insufficiency (MI), aortic stenosis (AS), and aortic regurgitation. Baseline risk factors and cardiac complications were compared. Multiple regression analysis was performed to study the association of NRVHD with stroke as the primary outcome in the subpopulation of APS hospitalizations. Results A total of 567600 adult patients hospitalized with diagnosis of APS were identified from the NIS 2017-2019 database. Among those, 33,095 had NRVHD with a mean age of 69 years. Of these, prevalence of males was 52.41% compared to females of 47.59%. In the cohort of APS, patients with NRVHD had a higher prevalence of coronary artery disease (43.78% vs 20.41%), diabetes mellitus (30.65% vs 27.56%), prior stroke (10.42% vs 7.78%) than those without valvular disorders. Among the APS population the most prevalent NRVHD were mitral insufficiency (MI), 2.45% and aortic stenosis (AS), 2.13%. In the cohort of NRVHD in APS hospitalizations, the odds of stroke was found to be 1.3 times higher with statistical significance (confidence interval (CI): 1.13-1.48, p &amp;lt;0.001) adjusted for relevant clinical and demographic risk factors such as tobacco abuse, CAD, diabetes mellitus, prior stroke. Conclusion This study shows 6.2% prevalence of NRVHD in APS population, of which MI and AS were common. NRVHD is also associated with higher odds of stroke in APS. Further studies are warranted in identifying the risk of stroke with NRVHD in APS population and emphasizing the need for early detection.

Are seronegative patients with rheumatoid arthritis and clinically suspect arthralgia properly represented in randomized clinical trials?

Rheumatoid arthritis (RA) is a chronic immuno-inflammatory disease whose outcomes can vary greatly from one patient to another. One of the main prognostic factors is the presence of serum autoantibodies, such as rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA). Indeed, when seropositive, patients with RA are at higher risk of radiographic progression, disability, and increased mortality. Moreover, while the introduction of the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria has allowed for an earlier diagnosis, studies on large early arthritis cohorts have also shown that these criteria are less capable of identifying seronegative patients, who are therefore at a higher risk of being diagnosed and treated late. In light of these, the major randomized controlled trials have mostly enrolled patients with autoantibody-positive disease. However, in recent years, it became evident that the two serotypes of RA differ significantly from many points of view. Alongside this, a greater understanding of the disease pathogenesis, particularly the presence of antibodies in patients' serum even before the onset of arthritis, has generated significant interest in exploring whether the disease could be prevented by treating patients in the pre-arthritis phases. Once again, emerging trials predominantly enroll subjects positive for RA autoantibodies, potentially overlooking seronegative individuals with arthralgia-at-risk.

Role of the Hemostasis and Thrombosis Unit in the Management of Patients with Acquired Hemophilia A

Acquired hemophilia A (AHA) is a rare autoimmune disease characterized by the presence of autoantibodies against coagulation factor VIII, leading to spontaneous hemorrhage in patients without a prior family or personal history of bleeding. This study describes the demographics, diagnosis, underlying disorders, bleeding characteristics, treatment, and outcomes of 41 AHA patients together with specific case reports. Diagnosis and treatment of these patients occurred between 2005 and 2023. The median age at diagnosis was 67.8 (range: 15-93) years. Among the 41 patients, 10 (24%) cases were idiopathic, 4 (10%) were postpartum, 18 (44%) involved autoimmune diseases, and 9 (22%) involved a diagnosis of cancer. The diagnostic delay exceeded 30 days in 15 of the 41 cases (36.5%). A total of 38 of the 41 (93%) patients presented with spontaneous bleeding, with mucocutaneous bleeding being the most common presentation (23/41, 56%). Four patients experienced postpartum bleeding. Clinical remission was achieved by 100% of patients and no patients died. Hemostatic and immunosuppressive therapy is essential in AHA, and it should be started as soon as possible in patients with bleeding. However, a significant delay in diagnosis was observed in these cases. The absence of mortality is likely attributable to the management of the disease within a specialized hemostasis and thrombosis unit, which offers a clinical ward, a specialized laboratory, and a dedicated ambulatory service. The Italian Society for the Study of Haemostasis and Thrombosis is working to secure recognition of this essential role in every hospital.

Prevalence & clinical outcome of autoimmune encephalitis versus viral encephalitis in children with acute encephalitis syndrome: A prospective observational study.

Background & objectives Acute encephalitic syndrome (AES), encompasses a wide spectrum of potential causes, clinical presentations, and outcomes. While infectious encephalitis is generally considered more prevalent, autoimmune encephalitis is emerging as a significant aetiology. Neuronal autoantibodies have been identified independently or in association with acute viral encephalitis. The primary objective of this study was to ascertain the prevalence and clinical manifestation of autoimmune encephalitis as well as of coexisting viral markers in children with AES. Methods This study was a prospective observational investigation conducted in a hospital setting. It involved enrolling children with AES who were admitted to specific tertiary hospitals. Children were subjected to examinations to detect the presence of viral markers and neuronal autoantibodies in both their blood and cerebrospinal fluid (CSF). All the participants received treatment based on established guidelines and was followed for six months for outcome assessment. Results During the study period, 867 children with AES were examined. Among these cases, 37 children (4.2%) were diagnosed with autoimmune encephalitis, and all of them tested positive for anti-NMDAR (N-methyl-D-aspartate receptor) antibodies. Evidence of viral infection was seen in 409 (47.1%) of cases, out of which nearly 254 (29.2%) children had detectable HSV IgM antibodies. Among the 37 children with autoimmune encephalitis, 25 (67.5%) had evidence of a viral trigger, with eight of them tested positive for HSV IgM antibodies. The clinical presentation of autoimmune-associated AES was similar to those with viral aetiology. Interpretation & conclusions Autoimmune encephalitis triggered by neurotropic (HSV) viral infection was more prevalent in this study than in the earlier reports. Typically, these children show positive responses to immunosuppressive treatments if administered promptly. It is hence advisable to assess children who exhibit behavioural issues and movement disorders for possible autoimmune encephalitis.

Is Idiopathic Granulomatous Mastitis a Subgroup of Systemic Lupus Erythematosus? A Preliminary Study

Objective: The study aimed to use the systemic lupus erythematosus risk probability index (SLERPI) to assess if patients with idiopathic granulomatous mastitis (IGM) meet the criteria for systemic lupus erythematosus (SLE). Methods: A total of 62 patients with IGM and 55 age- and sex-matched healthy controls (HC) were enrolled. The study included patients who were over 18 years old and had been diagnosed with IGM using a true-cut biopsy. The participants’ demographic, clinical, and laboratory data were recorded in detail. The presence of autoantibodies, such as RF, CCP, C3, C4, ANA, ENA profile, and Anti-dsDNA was documented. For the detection of SLE in IGM patients, we used the SLERPI (SLE risk probability index). Results: A total of 62 patients diagnosed with idiopathic granulomatous mastitis (age 35.22 ± 8.34, BMI 27.15 ± 3.41) were compared to 55 healthy controls (age 32.54 ± 8.67, BMI 26.97 ± 3.54). The present study assessed the performance of SLERPI in IGM, and SLERPI positivity was observed in 12 out of 62 (19.4%) IGM patients. There was a significant difference in arthritis and ANA levels in the SLERPI subgroups (p &lt; 001). Conclusions: The SLERPI index can be utilized to identify patients suspected of having systemic lupus erythematosus (SLE) in the IGM cohort.

Epigenetic trajectory predicts development of clinical rheumatoid arthritis in ACPA+ individuals: Targeting Immune Responses for Prevention of Rheumatoid Arthritis (TIP-RA).

The presence of autoantibodies to citrullinated protein antigens (ACPAs) in the absence of clinically-apparent inflammatory arthritis (IA) identifies individuals "at-risk" for developing future clinical rheumatoid arthritis (RA). However, it is unclear why some ACPA+ individuals convert to clinical RA while others do not. We explored the possibility in the Targeting Immune Responses for Prevention of Rheumatoid Arthritis (TIP-RA) study that epigenetic remodeling is part of the trajectory from an at-risk state to clinical disease and identifies novel biomarkers associated with conversion to clinical RA. ACPA-Controls, ACPA+ At-Risk, and Early RA individuals were followed for up to 5 years, including obtaining blood samples annually and at RA diagnosis. Peripheral blood mononuclear cells (PBMCs) were separated into CD19+ B cells, memory CD4+ T cells, and naïve CD4+ T cells using antibodies and magnetic beads. Genome-wide methylation within each cell lineage was assayed using the Illumina MethylationEPIC v1.0 beadchip. ACPA+ At-Risk participants who did or did not develop RA were designated "Pre-RA" or "Non-converters", respectively.Differentially methylated loci (DML) were selected using the Limma software package. Using the Caret package, we constructed machine learning models in test and validation cohorts and identified the most predictive loci of clinical RA conversion. Cross-sectional differential methylation analysis at baseline revealed DMLs that distinguish the Pre-RA methylome from ACPA+ Non-converters, the latter which closely resembled ACPA-Controls. Genes overlapping these DMLs correspond to aberrant NOTCH signaling and DNA repair pathways in B cells. Longitudinal analysis showed that ACPA-Control and ACPA+ Non-converter methylomes are relatively constant. In contrast, the Pre-RA methylome remodeled along a dynamic "RA methylome trajectory" characterized by epigenetic changes in active regulatory elements. Clinical conversion to RA, defined based on diagnosis, marked an epigenetic inflection point for cell cycle pathways in B cells and adaptive immunity pathways in naïve T cells. Machine learning revealed individual loci associated with RA conversion. This model significantly outperformed autoantibodies plus acute phase reactants as predictors of RA conversion. DNA methylation is a dynamic process in ACPA+ individuals at-risk for developing RA that eventually transition to clinical disease. In contrast, non-converters and controls have stable methylomes. The accumulation of epigenetic marks over time prior to conversion to clinical RA conforms to pathways that are associated with immunity and can be used to identify potential pathogenic pathways for therapeutic targeting and/or use as prognostic biomarkers.

Precise identification and tracking of HMGCR-reactive CD4+ T cells in the target tissue of patients with anti-HMGCR immune-mediated necrotising myopathy

BackgroundAnti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR)-positive immune-mediated necrotising myopathy (IMNM) is characterised by the presence of IgG autoantibodies against HMGCR and a strong association with specific HLA-DR alleles. Although these findings...

Autoantibodies Targeting Proteasome Subunit Alpha Type 1 in Autoimmune Podocytopathies.

The antibody against proteasome subunit alpha type 1 (PSMA1) is a podocyte autoantibody in idiopathic nephrotic syndrome (INS) children identified in our previous study. The aim of this study was to explore the characteristics of INS in children and the mechanism underlying its involvement in the development of INS. The levels of serum anti-PSMA1 autoantibodies in children were detected via protein microarray and compared among different disease groups. The recombinant PSMA1 protein was injected subcutaneously and intraperitoneally into mice to observe glomerular morphology and function. The PSMA1-knockdown and PSMA1-overexpressing cell lines were constructed from mouse podocytes, and their cytoskeleton and function were analyzed. Homozygous zebrafish with psma1 knockout were observed. The levels of serum anti-PSMA1 autoantibodies were higher in INS children and varied with urinary protein. In mice immunized with PSMA1, the presence of serum anti-PSMA1 autoantibody caused albuminuria and damage to the glomerular filtration membrane. Deficiency of PSMA1 impaired the podocyte cytoskeleton and physiological function. Complete deletion of psma1 caused edema, abnormal glomerular morphology and effacement of foot processes in zebrafish. PSMA1 played an important role in the maintenance of podocyte morphology and function.

6489 Type 1 Diabetes Mellitus And Multiple Sclerosis: A Case Report Showing The Concurrent Association Of Two Autoimmune Diseases

Abstract Disclosure: P.B. Singh: None. B. Sabates: None. A. Sharifzadeh: None. R.F. Rodriguez: None. Introduction: Both Type 1 Diabetes Mellitus (T1DM) and Multiple Sclerosis (MS) represent persistent autoimmune conditions. T1DM is characterized by the presence of specific autoantibodies targeting pancreatic β-cells. In MS, autoreactive cells mediate a demyelinating inflammatory response directed against the central nervous system. Despite differences in demographics and clinical characteristics, their common root in autoimmunity has led researchers to discover commonalities in genetic, environmental and immunological features. Case Presentation We present a case of a 40-year-old female with medical history of T1DM diagnosed at 7 years of age and MS diagnosed at 32 years of age. She presented to the hospital with clinical features of optic neuritis and symptoms of squeezing ribcage pressure consistent with acute MS exacerbation. After confirmatory neuroimaging, high-dose intravenous corticosteroids were initiated, and Endocrinology services were consulted for inpatient glycemic management. As the patient’s diabetes was treated via continuous subcutaneous insulin infusion (CSII), her pump settings were adjusted to maintain euglycemia during hospitalization. This case is reported to highlight and discuss the association between T1DM and MS. Discussion About 4-5% of the general population is affected by autoimmune disorders, among which T1DM and MS comprise a substantial portion. Multiple studies demonstrate the association and shared etiopathogenesis between T1DM and MS. One study revealed that the prevalence of T1DM is five times higher in patients with MS in comparison to the general population. In another prospective cohort study, individuals with T1DM had a three times higher chance of subsequently developing MS. Additionally, first-degree relatives of MS patients had a roughly 40% higher risk of developing T1DM. Women with T1DM had a 20-fold higher risk of having MS than women without the condition, per another study. As T-cell mediated autoimmune disorders, both T1DM and MS are characterized by autoantigen specific T1-helper cell responses, decreased T-cell suppressor activity, and the presence of various autoantibodies, some of which are seen in both diseases. One study showed that autoreactive T cells could target both pancreatic islet and central nervous system autoantigens in patients with MS, patients with T1DM, and relatives of patients with T1DM. Since MS- and T1DM-associated HLA haplotypes differ between populations, HLA class II alleles per se may not alone be responsible for disease susceptibility. It is suggested that variation at other non-HLA class II loci and/or unknown environmental factors might contribute significantly to the co-occurrence of these 2 diseases. In conclusion, individuals who already have one autoimmune condition are more likely to have other autoimmune conditions, with T1DM and MS being associated more often than expected. Presentation: 6/2/2024