anti-SSB Antibodies Research Articles

Meta-analysis of mortality-associated factors in primary Sjögren's syndrome patients with interstitial lung disease.

The study aims to conduct a meta-analysis on 5-year survival rate and mortality-related factors in the patients with primary Sjögren's syndrome concomitant with interstitial lung disease (pSS-ILD). Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched various platforms and databases until November 22, 2023. We used the Newcastle-Ottawa Scale (NOS) for quality assessment and extracted study characteristics and effect sizes. The pooled 5-year survival rate, hazard ratios (HRs), and the corresponding 95% confidence intervals (95% CIs) were then calculated. A p-value of less than 0.05 was considered statistically significant. Patients with pSS-ILD. Mortality in patients with pSS-ILD. Out of 188 articles, seven met the inclusion criteria. The meta-analysis estimated a 5-year survival rate of 82% (73%-91%). Mortality-related factors estimated by the meta-analysis included older age (HRs = 1.06, 95% CI 1.03-1.09, P < 0.0001), history of smoking (HRs = 3.44, 95% CI 2.14-5.53, P < 0.00001), anti-SSA antibody positivity (HRs = 0.41, 95% CI 0.20-0.85, P = 0.02), anti-SSB antibody positivity (HRs = 0.42, 95% CI 0.18-0.98, P = 0.04), reduced forced vital capacity (FVC; HRs = 0.96, 95% CI 0.95-0.98, P < 0.0001), reduced 6-min walk distance (6MWD; HRs = 0.99, 95% CI 0.99-1.00, P = 0.0008), presence of a reticular abnormality (HRs = 3.03, 95% CI 1.54-5.95, P = 0.001), and decreased arterial partial pressure of oxygen (PaO2) levels (HRs = 0.99, 95% CI 0.97-1.00, P = 0.04). The 5-year survival rate for pSS-ILD is 82%. Older age, history of smoking, anti-SSA antibody negativity, anti-SSB antibody negativity, reduced FVC, reduced 6MWD, presence of a reticular abnormality, and decreased PaO2 levels increase the mortality risk in pSS-ILD.

Epidemiology of Sjogren's syndrome in a sample of the Egyptian population: a cross-sectional study.

To investigate the prevalence of Sjögren's syndrome (SS) and the associated factors in a sample of the Egyptian population. This cross-sectional study obtained data by screening subjects from several hospitals in different governorates across Egypt. Demographic and health data were collected including symptoms and type of Sjögren's syndrome, associated autoimmune diseases, the presence of specific autoantibodies and associated malignancies. The study analysed 7960 participants and 64 (0.80%) had SS. Of these, 22 (34.38%) had primary SS and 42 patients (65.63%) had secondary SS. For the total study cohort, the prevalence of primary and secondary SS was 0.28% and 0.53%, respectively. There was a higher prevalence of SS in females compared with males and SS was more common in the fifth and sixth decades. All patients with SS complained of oral and ocular dryness. The most common concomitant autoimmune disease was rheumatoid arthritis. Anti-SSA (Ro) and anti-SSB (La) antibodies were the most frequently associated autoantibodies. Only two patients had non-Hodgkin's lymphoma. This was the first study to describe the prevalence of SS in Egypt. SS is not a rare disease in Egypt, so raising awareness of SS in both patients and healthcare professionals is very important.

Correlation between neuropsychiatric systemic lupus erythematosus and immunological markers: a real-world retrospective study.

This study aimed to investigate disparities in clinical profiles and autoantibody patterns between patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE) in a cohort and to identify risk factors associated with NPSLE in the Chinese population. SLE patients were retrospectively reviewed from two tertiary hospitals. The relationships between NPSLE and immunological biomarkers were explored. Among the 945 SLE patients, 75 (7.94%) were diagnosed with NPSLE. The most prevalent NP manifestations involved cognitive disorder (30.67%), headache (26.67%), seizure disorder (26.67%), and psychosis (26.67%).We observed significant associations between psychosis and anti-β2GPI antibodies (F = 6.092, p = 0.015), polyneuropathy and anti-Scl70 antibodies (F = 20.161, p < 0.001), demyelinating syndrome and anti-cardiolipin antibodies (F = 6.637, p = 0.011), myasthenia gravis and anti-RNP (F = 5.864, p = 0.017), and anti-Smith antibodies (F = 5.096, p = 0.026). Multivariate logistics analysis showed that anti-prothrombin (aPT) IgM antibodies (OR = 10.985, CI 1.279-94.343, p = 0.029), age (OR = 1.169, CI 1.032-1.325, p = 0.014), and serum creatinine (SCr) (OR = 1.014, CI 1.003-1.025, p = 0.009) were independent risk factors of NPSLE, while anti-Sjogren syndrome antigen B (SSB) antibodies (OR 0.023, CI 0.002-0.622, p = 0.023) and high complement C3 (OR = 0.001, CI 0-0.045, p < 0.001) indicated reduced risk of NPSLE. Various neuropsychiatric manifestations in SLE were found to be correlated with specific autoantibodies. Independent risk factors for NPSLE included aPT IgM antibodies, age, and elevated serum creatinine, while the absence of anti-SSB antibodies and low complement C3 levels were associated with increased risk. •Significant associations were found between specific autoantibodies and neuropsychiatric symptoms, shedding light on potential biomarkers for predicting and understanding NPSLE. •The study identifies independent risk factors for NPSLE in the Chinese population, including the presence of anti-prothrombin IgM antibodies, older age, elevated serum creatinine, and lower complement C3 levels.

Clinical characteristics and labial gland pathological features in children with systemic lupus erythematosus complicated by Sjögren's syndrome

To study the clinical manifestations, laboratory features, and labial gland pathological features in children with systemic lupus erythematosus (SLE) complicated by Sjögren's syndrome (SS). A retrospective analysis was conducted on 102 children with SLE who underwent labial gland biopsies at Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2022. The children were divided into two groups based on the presence of SS: the SLE with SS group (SLE-SS; 60 children) and the SLE-only group (42 children). According to the focus score (FS) of the labial glands, children in the SLE-SS group were further subdivided into FS≥4 subgroup (26 children) and FS<4 subgroup (34 children). The clinical data of the groups were compared. Compared to the SLE-only group, children in the SLE-SS group had less skin and mucosal involvement, were more likely to have positive anti-SSA and anti-SSB antibodies, and had higher levels of rheumatoid factor (P<0.05). There was no significant difference in treatment protocols between the two groups (P>0.05). Compared to the FS<4 subgroup, the FS≥4 subgroup had more frequent musculoskeletal involvement (P<0.05), but there was no significant difference in SLE disease activity or other major organ involvement between the subgroups (P>0.05). Children with SLE complicated by SS are less likely to have skin and mucous membrane involvement and exhibit specific serological characteristics. The SLE-SS children with an FS≥4 are more likely to experience musculoskeletal involvement. However, FS is not associated with disease activity or other significant organ damage.

The titers of antinuclear antibodies are associated with the degree of inflammation and organ damage in Primary Sjögren's Syndrome

Primary Sjögren’s Syndrome (pSS) falls within the category of connective tissue diseases, characterized by the presence of autoantibodies such as antinuclear antibodies (ANA). However, according to the classification criteria for pSS, some patients may exhibit a negative result for autoantibodies. Patients with a negative result for autoantibodies may lack typical features of connective tissue diseases, and the immunological state as well as the extent of organ involvement and damage may differ from those with positive autoantibodies. This study aims to compare the clinical phenotypes of patients with positive and negative autoantibodies, providing insights for disease classification and treatment selection for clinicians. Patients with pSS were grouped based on the presence and titers of their autoantibodies. Subsequently, differences in organ damage and laboratory indicators were compared between these groups, aiming to analyze the value of autoantibody titers in assessing the condition of pSS. (1) Patients with positive ANA exhibited elevated levels of inflammatory indicators, including ESR, IgG levels, lip gland biopsy pathology grade, and overall organ involvement, in comparison with patients with negative ANA (P < 0.05). Furthermore, ANA-positivity correlated with a higher occurrence of multi-organ damage, particularly affecting the skin, mucous membranes, and the hematological system (P < 0.05). (2) As ANA titers increased, patients demonstrated elevated levels of IgG and an escalation in organ involvement (P < 0.05). (3) Patients in the positive autoantibody group (positive for antinuclear antibodies, anti-SSA, or anti-SSB antibodies) had higher IgG levels compared to the negative group (P < 0.05). (4) Patients with positive anti-SSA and anti-SSB antibodies exhibited higher levels of inflammatory indicators and IgG compared to other patients (P < 0.05); however, no significant differences were observed in terms of organ involvement and organ damage. Patients with positive ANA in pSS typically exhibit higher levels of inflammation and an increased likelihood of experiencing multi-organ damage. Furthermore, as the ANA titers increase, both inflammation levels and the risk of multi-organ damage also escalate. Additionally, the presence of anti-SSA and anti-SSB antibodies may contribute to an elevated risk of increased inflammation levels, but does not increase the risk of organ damage.

Neonatal lupus erythematosus as a rare trigger of gastrointestinal involvement in neonates

Cutaneous and cardiac involvement in neonatal lupus erythematosus (NLE) has been extensively studied; however, gastrointestinal system involvement (GSI) remains unexplored. This study aimed to investigate the clinical features of GSI in patients with NLE with a particular focus on feeding intolerance (FI) and diarrhea. We conducted a retrospective analysis of the clinical data of patients diagnosed with NLE at the Children’s Hospital of Soochow University between 2011 and 2022. In this study, of 39 patients diagnosed with NLE, 27 presented with GSI. 9 patients who presented with FI or diarrhea as the primary manifestation were positive for anti-SSA antibody, and 5 were dual positive for anti-SSA and anti-SSB antibodies. Among the mothers of the NLE patients with GSI, 18 had systemic lupus erythematosus, 3 had Sjogren’s syndrome, 2 had mixed connective tissue disease, and one each had autoantibody abnormalities and photosensitivity symptoms; 4 mothers denied having any autoimmune disease. In this study, 69.23% of patients with NLE exhibited GSI, which was linked to hypocomplementemia and anti-SSA antibodies. Thus, clinicians should remain vigilant for NLE in neonates, particularly when accompanied with rash and other organ dysfunction and when the high-risk factors of FI and diarrhea have been excluded.

TAFRO syndrome is associated with anti-SSA/Ro60 antibodies, in contrast to idiopathic castleman disease

TAFRO syndrome is an acute systemic inflammatory disease characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis/renal dysfunction, and organomegaly. There have been increasing reports that TAFRO is a disease distinct from idiopathic multicentric Castleman disease and that TAFRO patients may be positive for anti-SSA antibodies. To assess anti-SSA antibody positivity and the clinical characteristics of the two diseases, we retrospectively compared 7 TAFRO and 10 iMCD patients in our hospital. The mean age of onset of TAFRO and iMCD was 48.0 (interquartile range [IQR], 41–53) and 45.0 (IQR, 35–53) years, respectively. The TAFRO and iMCD groups had 6 (86%) and 4 (40%) male patients, respectively, and the following pretreatment laboratory values: platelet count, 3.8 (IQR, 2.2–6.4) and 35.5 (IQR, 22.2–42.8) × 104/μL, respectively; C-reactive protein, 10.2 (IQR, 6.8–21.4) and 9.5 (IQR, 6.2–13.6) mg/dL, respectively; IgG, 1431 (IQR, 1112–1815) and 4725 (IQR, 3755–5121) mg/dL, respectively. RNA immunoprecipitation (5 cases for anti-SSA) or protein array (5 cases for anti-SSA/Ro60) detected anti-SSA antibodies in six (86%) TAFRO patients but not in iMCD patients; it did not detect anti-SSB antibodies in any of the patients. None of the patients were diagnosed with Sjögren syndrome. All iMCD patients treated with tocilizumab (TCZ) responded well. Meanwhile, two of six TAFRO patients treated with TCZ showed inadequate responses; thus, both patients were switched to rituximab, following which they achieved remission. TAFRO and iMCD have different clinical features. TAFRO may be categorized as a severe phenotype of the anti-SSA antibody syndrome.

Clinical value of chemiluminescence method for detection of antinuclear antibody profiles.

Antinuclear antibodies (ANAs) are crucial in diagnosing autoimmune diseases, mainly systemic lupus erythematosus (SLE). This study aimed to compare the performance of chemiluminescence assay (CLIA) and line immunoassay (LIA) in detecting ANAs in patients with autoimmune diseases, evaluate their diagnostic accuracy for SLE, and develop a novel diagnostic model using CLIA-detected antibodies for SLE. Specimens from patients with autoimmune diseases and physical examination specimens were collected to parallel detect specific antibodies. Individual antibodies' diagnostic performance and a model combining multiple antibodies were assessed. The findings provide valuable insights into improving the diagnosis of SLE through innovative approaches. To compare the performance of CLIA and LIA in detecting ANAs in patients with autoimmune diseases, assess their accuracy for SLE, and develop a novel diagnostic model using CLIA-detected antibodies for SLE. Specimens have been obtained from 270 patients with clinically diagnosed autoimmune disorders, as well as 130 physical examination specimens. After that, parallel detection of anti-double-stranded DNA (dsDNA) antibody, anti-histone (Histone) antibody, anti-nucleosome (Nuc) antibody, anti-Smith (Sm) antibody, anti-ribosomal P protein (Rib-P) antibody, anti-sicca syndrome A (Ro60) antibody, anti-sicca syndrome A (Ro52) antibody, anti-sicca syndrome (SSB) antibody, anti-centromere protein B (Cenp-B) antibody, anti-DNA topoisomerase 1 (Scl-70) antibody, anti-histidyl tRNA synthetase (Jo-1) antibody, and anti-mitochondrial M2 (AMA-M2) antibody was performed using CLIA and LIA. The detection rates, compliance rates, and diagnostic performance for SLE were compared between the two methodologies, followed by developing a novel diagnostic model for SLE. CLIA and LIA exhibited essentially comparable detection rates for anti-dsDNA antibody, anti-Histone antibody, anti-Nuc antibody, anti-Sm antibody, anti-Rib-P antibody, anti-Ro60 antibody, anti-Ro52 antibody, anti-SSB antibody, anti-Cenp-B antibody, anti-DNAScl-70 antibody, anti-Jo-1 antibody and anti-AMA-M2 antibody (P > 0.05). The two methods displayed identical results for the detection of anti-dsDNA antibody, anti-Histone antibody, anti-Nuc antibody, anti-Sm antibody, anti-Ro60 antibody, anti-Ro52 antibody, anti-SSB antibody, anti-Cenp-B antibody, anti-Scl-70 antibody, and anti-AMA-M2 antibody (Kappa > 0.7, P < 0.05), but showed a moderate agreement for the detection of anti-Rib-P antibody and anti-Jo-1 antibody (Kappa = 0.671 and 0.665; P < 0.05). In addition, the diagnostic performance of these antibodies detected by both methods was similar for SLE. The diagnostic model's area under the curve values, sensitivity, and specificity, including an anti-dsDNA antibody and an anti-Ro60 antibody detected by CLIA, were 0.997, 0.962, and 0.978, respectively. These values were higher than the diagnostic performance of individual antibodies. CLIA and LIA demonstrated excellent overall consistency in detecting ANA profiles. A diagnostic model based on CLIA-detected antibodies can successfully contribute to developing a novel technique for detecting SLE.

Association between endothelin-1 and systemic lupus erythematosus: insights from a case–control study

Systemic lupus erythematosus (SLE) is a chronic rheumatic disorder. Endothelin-1, a vasoconstrictor, belongs to the endothelin family and is associated with vascular-related damages. To date, association between ET-1 and pathogenesis of SLE remains unclear. This case–control study was carried out by 314 SLE, 252 non-SLE diseases patients and 500 healthy controls. Serum ET-1, CCN3, IL-28B levels were detected by ELISA, and ET-1 gene polymorphisms (rs5369, rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs4145451, rs6458155, rs9369217) were genotyped with Kompetitive Allele-Specific PCR. SLE patients had high levels of ET-1, which were correlated with some clinical, laboratory features. Serum CCN3, IL-28B levels were higher in SLE patients, and ET-1 levels were positively correlated with the two cytokines. Rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs6458155 and rs2070699 were associated with SLE risk. Rs2070699 (T, TT) was related to SLE patients with alopecia. Rs5370 (T, TT, TG), rs1476046 (G,GA), rs2071942 (G,GA) and rs2071943 (G,GA) were associated with SLE patients with pericarditis, pyuria and fever manifestation, respectively. Rs3087459 (CC) and rs9369217 (TC) were related to SLE patients with positive anti-SSB antibody. Rs5369 (AA) was associated with IgG and CRP levels in SLE patients. In conclusion, elevated serum ET-1 in SLE patients may be a potential disease marker, and its gene polymorphisms were related to SLE susceptibility.

Endothelial Dysfunction in Primary Sjögren's Syndrome: Correlation with Serum Biomarkers of Disease Activity.

To assess the relationship between endothelial dysfunction and serum cytokines, anti-SSA and anti-SSB antibodies, beta-2 microglobulin levels, focus score and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in primary Sjögren's syndrome (pSS) patients. The study included 90 patients with pSS and 45 healthy subjects, matched for age and gender, as controls. Serum beta-2 microglobulin, total cholesterol, HDL-cholesterol, triglycerides, TNF-α, and IL-6 were analyzed in both the groups. Patients with pSS were also tested for antinuclear antibodies, anti-SAA (anti-Sjögren's syndrome-related antigen A) antibodies, anti-SSB (anti-Sjögren syndrome related antigen B) antibodies, and focus score (the histopathologic one, based on minor salivary gland biopsy). Endothelial dysfunction was assessed by means of flow-mediated dilation (FMD) in the brachial artery. Data are presented as mean ± standard deviation. Statistical analysis was performed using the t-test and the Pearson's correlation. Differences were considered to be statistically significant if the value of p < 0.05. Endothelial dysfunction was identified in pSS patients (p < 0.00001). The serum levels of cytokines (TNF-α, respective IL-6) and beta-2 microglobulin were increased in pSS patients compared with controls (p < 0.00001). Endothelial dysfunction (expressed as FMD%) was correlated with focus score, ESSDAI, levels of anti-SSA and anti-SSB antibodies, beta-2 microglobulin, IL-6, and TNF-α, with statistical significance. Endothelial dysfunction is present in pSS patients and is associated with a high focus score and activity as well as increased concentrations of antibodies, pro-inflammatory cytokines, and beta 2-microglobulin.

Characteristics of primary Sjögren's syndrome-associated peripheral nervous system lesions.

The aim of this study is to investigate potential risk factors associated with peripheral nervous system lesions in primary Sjögren's syndrome (pSS) through a retrospective analysis of clinical manifestations, examination characteristics, and clinical electrophysiological features. A retrospective case-control study was conducted at Nanfang Hospital, including 108 patients diagnosed with pSS following the criteria revised by the American College of Rheumatology in 2016. The study spanned from January 2015 to October 2020. The patient cohort was divided into two groups, an experimental group (N = 27) consisting of patients with primary Sjögren's syndrome-peripheral nervous system lesions (pSS-PNS), and a control group (N = 81) comprising patients without peripheral neurological impairment, i.e., primary Sjögren's syndrome-non peripheral nervous system lesions (pSS-nPNS). The results showed a significant correlation between immunoglobulin G (IgG), α-Fodrin immunoglobulin G (α-FIgG), platelet counts (PLT), dry mouth and peripheral neuropathy of Sjogren's syndrome (p < 0.01). The research also revealed that α-FIgG (OR 2.03; 95% CI 1.14-3.64), IgG (OR 1.23; 95% CI 1.06-1.42), and PLT (OR 1.01; 95% CI 1.00-1.01) were identified as risk factors for the onset of peripheral neuropathy of Sjogren's syndrome, while dry mouth had a negative correlation (OR 0.08; 95% CI 0.02-0.40). Remarkably, the total risk assessment of the independent variables demonstrated a high AUC (95%CI) of 0.923 (0.861-0.986; p < 0.001), indicating an excellent prediction of pSS-PNS occurrence through the ROC analysis. Additionally, high platelet counts and strong positive anti-SSB antibody titer were found to be risk factors for dual motor and sensory nerve damages among pSS-PNS patients. IgG, α-FIgG, and PLT were identified as independent risk factors for patients with pSS-PNS. The likelihood of peripheral neuropathy appeared to increase in tandem with the elevated levels of above three factors. Interestingly, we found that dry mouth might play a protective role in this context. Our study further noted that both high platelet counts and strong positive anti-SSB antibody titer may be associated with increased risk of both motor and sensory nerve involvement in pSS-PNS patients. These findings have significant implications for both the etiologies and therapeutics of pSS-PNS.

Primary Sjögren’s syndrome misdiagnosed as Mikulicz’s disease: a case report

BackgroundSjögren’s Syndrome (SS) is an inflammatory autoimmune disease, and Mikulicz’s disease (MD) is a lymphoproliferative disorder. Both MD and SS are more common in middle-aged female, and the dry eyes could be presented in both of them with different degree. The MD patients are characterized by symmetrical swelling of the lacrimal glands which also can occur in the early stage of SS. And the imaging findings between early stage of SS and MD are lack of specificity. Therefore, SS and MD have similarities in the clinical manifestations, imaging and pathological findings and are confused in diagnosis.Case presentationA 51-year-old female patient presented with bilateral swelling of the upper eyelids for 2 years. She also reported having dry mouth and dry eyes which could be tolerated. The Schirmer’s test result is positive and the laboratory tests indicate serum total IgG increased. In the bilateral lacrimal gland area could palpate soft masses. The orbital magnetic resonance imaging (MRI) examination showed bilateral lacrimal gland prolapse. While the histopathological result was considered as MD. The immunohistochemical (IHC) staining results were positive for IgG and negative for IgG4. To clarify the diagnosis, SS-related laboratory tests were performed: anti-SSA antibody (+++), anti-SSB antibody (+++), anti-Ro-52 antibody (+++). With a comprehensive consideration, the final diagnosis was SS.ConclusionWhen the clinical manifestations are atypical, it is necessary to pay attention to the differential diagnosis of SS and MD.

Diagnostic dilemma: Multiple Autoimmune Syndrome versus incomplete Graham-Little-Piccardi-Lassueur Syndrome overlap mixed connective tissue disease

Objectives. We present a very rare case of incomplete Graham-Little-Piccardi-Lassueur syndrome (GLPLS) overlap with Mixed Connective Tissue Disease (MCTD) versus Multiple Autoimmune Syndrome (MAS). Case Presentation. A 53- year-old female with a long history of more than two years of patchy hair loss on scalp like “footprints in the snow”, partial loss of eyebrows' hair, face erythema, scaly atrophied red/brown patches on face, grouped follicular papules 2-3 mm in diameter with a pointed or hair-like horny spine extending approximately 1-2 mm around the tip of the follicle on lumbar area. The histopathological results from biopsies of scalp and lumbar areas confirmed the clinical diagnosis of cicatricial alopecia induced by lichen plan pilaris (LPP) and also presence of lichen spinulosus (LS) on lumbar area. The description provided by pathologist is however borderline regarding so called interface dermatosis like chronic cutaneous lupus erythematous (CCLE) or Pseudopelade of Brocq (PPB) as the end stage of CCLE or LPP. Blood tests showed both Antinuclear antibodies and U1-nRNP in high titers and the absence of anti-Sm, anti SS-A, anti SS-B and anti-dsDNA antibodies, and also peculiar antibody patterns of MCTD. Outcome. After thorough investigation, MCTD was proven by antibodies results. After one year of treatment a lot of clinical features dramatically responded under therapy. Conclusions. Clinical manifestations in the pathology with strictly cutaneous or systemic localization in conjunction or overlap with other autoimmune diseases (grouped in the MAS) represent a rare diagnostic in daily practice.

Serological and clinical associations of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus

To study the clinical significance of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus (SLE), we enrolled 526 new-onset patients who met the 1997 Updated American College of Rheumatology SLE Classification Criteria for a retrospective cohort study. Chi-square test and Wilcoxon rank-sum test were used to detect the relationship of autoantibodies with clinical manifestations and serological results respectively. Our results demonstrated that the positive rate of anti-ribosomal P protein (anti-P) antibody in female patients was higher than that in male patients (41.2% vs. 22%, P = 0.008). Patients with anti-SSB (43.95 ± 73.12 vs. 40.92 ± 75.75, P = 0.004; 63.93 ± 103.56 vs. 55.06 ± 120.84, P = 0.008 respectively) antibodies had higher levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), whereas those with anti-P antibody (28.90 ± 25.70 vs. 50.08 ± 93.00, P = 0.014; 38.51 ± 48.19 vs. 69.95 ± 142.67, P = 0.047, respectively) had lower levels of them. Anti-dsDNA antibody (P = 0.021) was associated with pulmonary arterial hypertension (PAH). The patients with anti-Ro60 (P = 0.044), anti-P (P = 0.012) and anti-dsDNA (P = 0.013) antibodies were less likely to develop Interstitial lung disease. Anti-SmRNP antibody was correlated to lower prevalence of neuropsychiatric symptoms (P = 0.037), and patients with anti-centromere antibody (ACA) were more likely to develop serositis (P = 0.016).We identified five clusters of SLE-related autoantibodies, confirmed previously reported associations of autoantibodies, and discovered new associations.

#5348 THE EFFECTS OF RITUXIMAB IN NON-HCV-RELATED MIXED CRYOGLOBULINEMIC VASCULITIS

Abstract Background and Aims Remarkable results in severe HCV-related cryoglobulinemic vasculitis have been obtained with Rituximab. Details of the clinical characteristics and effective treatment of non HCV-related cryogloulinemic syndromes are presently lacking. Method This paper reports on a prospective single-Center open study aimed at evaluating the clinical presentation and effects of Rituximab administered alone in patients with severe non HCV-related cryoglobulinemic syndrome Results The study group included 11 patients followed for at least 6 months. Three patients had type I cryoglobulinemia, 6 had type II and the remaining 2 patients had type III. Mean cryocrit was 2.5%. Four out of 11 patients had symptomatic sicca complex with anti-SSA (Ro)/anti SSB (La) antibodies. All 11 patients presented with biopsy-proven renal involvement, 4 out of 11 with leukocytoclastic vasculitis, and 8 with involvement of the peripheral nervous system. Renal biopsy revealed diffuse membranoproliferative glomerulonephritis (MPGN) in 9 out of 11 patients. Extracapillary proliferation and necrosis of the glomerular tuft was observed in 1 of these 9 cases. Interstitial nephritis together with mesangial expansion and capillary immune deposits were observed in 1 patient. Prevalent interstitial fibrosis and glomerular sclerosis were detected in the remaining case. Patients underwent treatment with rituximab alone. After 6 months we observed a remarkable improvement in the necrotizing skin ulcers and a substantial amelioration of the electrophysiological parameters of motor and sensory peripheral neuropathy. Improvement in both renal function (from 2.8 to 1.4 mg/dl, p &amp;lt; 0.001) and proteinuria (from 4.2 g/24 to 0.4 g/24 h, p &amp;lt; 0.001) was found in 10 out of 11 patients, while 1 could not be fully treated because of a severe infusion reaction and sudden development of anti-Rituximab antibodies. Good renal response was confirmed at the end of follow-up (38.4 months). Three patients had a relapse at 6, 12, and 48 months, respectively. Conclusion In our cohort the administration of 4 once-weekly infusions of Rituximab followed by 2 more infusions after 1 and 2 months proved to be effective in the management of these rare patients.

#4323 A RARE CASE OF MEMBRANOUS NEPHROPATHY AS THE INITIAL PRESENTATION OF SJöGREN SYNDROME

Abstract Introduction Primary Sjögren's syndrome (pSS) is an autoimmune disorder characterized by lymphocytic infiltrates in exocrine glands, most commonly manifesting as dry eyes and mouth. Even though extra glandular involvement can occur in Sjögren, renal involvement is rare. It affects less than 10% of the patient population, with tubulointerstitial nephritis being the usual presentation. Glomerular involvement and, in particular, membranous nephropathy are not commonly encountered. We describe a rare case of membranous nephropathy as the initial presentation of Primary Sjögren's syndrome. Case history A 21-year-old female with a history of sickle cell trait presented to our emergency department with one week history of anasarca. Vital signs were unremarkable, and the physical exam was significant for a 2+ pitting edema of bilateral upper and lower extremities. Initial investigation revealed acute kidney injury (Creatinine 2.9 mg/dl from normal baseline), nephrotic range proteinuria of 6 grams on 24-hour urine collection, and hypoalbuminemia (serum albumin 1.5 mg/dl). Immunological workup showed positive ANA (speckled), strongly positive anti-SSA, borderline elevated anti-SSB, negative anti-PLA2R, negative cryoglobulins, negative anti-dsDNA, and negative anti-Smith antibody (Figure 1). Renal biopsy (Figure 2) revealed membranous nephropathy with acute tubular necrosis (ATN). PLA2R staining was negative. We attributed acute kidney injury to ATN and proteinuria to membranous nephropathy. Negative serologies and renal biopsy findings ruled out systemic Lupus. The patient was therefore diagnosed with membranous nephropathy secondary to pSS. The patient was started on Mycophenolate mofetil and steroid taper with an improvement of proteinuria and anasarca and currently follows at our clinic. Discussion Glomerular involvement is rare, and when involved, it is membranoproliferative glomerulonephritis (MPGN) associated with B-cell activation and positive cryoglobulins. Membranous nephropathy is rare with primary Sjögren syndrome. In our patient, a negative anti-PLA2R goes against primary membranous nephropathy. A negative anti-dsDNA and anti-Smith and biopsy findings essentially rule out Lupus nephritis, leaving Sjögren induced secondary membranous nephropathy as the most likely diagnosis. A literature search revealed few described cases of membranous nephropathy as the presenting feature of pSS with later development of sicca symptoms and progression of renal disease to MPGN. Interestingly, our patient had no sicca symptoms at the presentation time. Occult salivary gland involvement has been described in some of these patients; however, our patient deferred salivary gland biopsy. The management of renal disease in pSS has yet to be well described because of its rarity. Rituximab has shown the most benefit in patients with pSS who have positive cryoglobulins and associated MPGN. Steroids and mycophenolate mofetil (MMF) are other possible agents that can be tried. Given that experience, we started on steroids and MMF with an excellent response to treatment indicated by improvement in proteinuria. Conclusion This case adds to the limited available literature on membranous nephropathy as the initial manifestation of pSS. Although the European Alliance of Associations for Rheumatology (EULAR) criteria strongly emphasizes sicca symptoms and glandular involvement in pSS, the possibility of a small subset of pSS patients who present with early renal involvement with latent glandular findings needs to be recognized.

Increased METTL3 expression and m6A RNA methylation may contribute to the development of dry eye in primary Sjögren’s syndrome

BackgroundPrimary Sjögren’s syndrome (pSS) is a chronic autoimmune disorder defined by xerostomia and keratoconjunctivitis sicca, and its etiology remains unknown. N6-methyladenosine (m6A) is the predominant posttranscriptional modification in eukaryotic mRNAs and is dynamically regulated by m6A regulators. Dysregulation of m6A modification is closely associated with several autoimmune disorders, but the role of m6A modification in pSS remains unknown. This study investigated the potential role of m6A and m6A-related regulators in pSS patients with dry eye.MethodsThis cross-sectional study included forty-eight pSS patients with dry eye and forty healthy controls (HCs). Peripheral blood mononuclear cells (PBMCs) were isolated, and the level of m6A in total RNA was measured. The expression of m6A regulators was determined utilizing real-time PCR and western blotting. The serological indicators detected included autoantibodies, immunoglobulins (Igs), complement factors (Cs), and inflammatory indicators. Dry eye symptoms and signs were measured, including the ocular surface disease index, Schirmer’s test (ST), corneal fluorescein staining score (CFS), and tear break-up time. Spearman’s correlation coefficient was employed to assess the associations of m6A and m6A-related regulator expression with clinical characteristics.ResultsThe expression level of m6A was markedly increased in the PBMCs of pSS patients with dry eye compared to HCs (P value<0.001). The relative mRNA and protein expression levels of the m6A regulators methyltransferase-like 3 (METTL3) and YT521-B homology domains 1 were markedly elevated in pSS patients with dry eye (both P value<0.01). The m6A RNA level was found to be positively related to METTL3 expression in pSS patients (r = 0.793, P value<0.001). Both the m6A RNA level and METTL3 mRNA expression correlated with the anti-SSB antibody, IgG, ST, and CFS (all P values < 0.05). The m6A RNA level was associated with C4 (r = -0.432, P value = 0.002), while METTL3 mRNA expression was associated with C3 (r = -0.313, P value = 0.030).ConclusionsOur work revealed that the upregulation of m6A and METTL3 was associated with the performance of serological indicators and dry eye signs in pSS patients with dry eye. METTL3 may contribute to the pathogenesis of dry eye related to pSS.

Anti-SSA/SSB-negative primary Sjögren’s syndrome showing different clinical phenotypes: a retrospective study of 934 cases

BackgroundCurrently, only a few studies have described the general characteristics of patients with primary Sjögren’s syndrome (pSS) who tested negatives for anti-SSA and anti-SSB antibodies. We aimed to further investigate the clinical characteristics of these patients in a large sample.MethodsData from patients with pSS who were treated at a tertiary hospital in China between 2013 and 2022 were retrospectively analyzed. Clinical characteristics of the patients were compared between those with and without anti-SSA and anti-SSB antibody negativity. Factors associated with anti-SSA and anti-SSB negativity were identified by logistic regression analysis.ResultsOverall, 934 patients with pSS were included in this study, among whom 299 (32.0%) tested negative for anti-SSA and anti-SSB antibodies. Compared with patients testing positive for anti-SSA or anti-SSB antibodies, that testing negative for the two antibodies had a lower proportion of females (75.3% vs. 90.6%, p < 0.001) and thrombocytopenia (6.7% vs. 13.6%, p = 0.002), but a higher proportion of abnormal Schirmer I tests (96.0% vs. 89.1%, p = 0.001) and interstitial lung disease (ILD) (59.2% vs. 28.8%, p = 0.001). Anti-SSA and anti-SSB negativity was positively associated with male sex (odds ratio [OR] = 1.86, 95% confidence interval [CI]: 1.05, 3.31), abnormal Schirmer I tests (OR = 2.85, 95% CI: 1.24, 6.53), and ILD (OR = 2.54, 95% CI: 1.67, 3.85). However, it was negatively related to thrombocytopenia (OR = 0.47, 95% CI: 0.24, 0.95).ConclusionApproximately one third of pSS patients had anti-SSA and anti-SSB negativity. pSS patients testing negative for anti-SSA and anti-SSB showed a higher risk of abnormal Schirmer I tests and ILD, but a lower risk of thrombocytopenia.

Salivary gland ultrasound in clinical practice: What is its real usefulness?

BackgroundSalivary gland ultrasound (SGU) provides information about structural gland abnormalities that can be graded and used for primary Sjögren's syndrome (pSS) diagnosis. Its potential role as a prognostic marker for detecting patients at high risk of lymphoma and extra-glandular manifestations is still under evaluation. We aim to assess the usefulness of SGU for SS diagnosis in routine clinical practice and its relationship with extra-glandular involvement and lymphoma risk in pSS patients. MethodsWe designed a retrospective observational single-center study. Data was collected using the electronic health records of patients referred to an ultrasound outpatient clinic for evaluation over a 4-year period. Data extraction included demographics, comorbidities, clinical data, laboratory tests, SGU results, salivary gland (SG) biopsy, and scintigraphy results. Comparisons were made between patients with and without pathological SGU. The external criterion for comparison was the fulfillment of the 2016 ACR/EULAR pSS criteria. ResultsA total of 179 SGU assessments were included from this 4-year period. Twenty-four cases (13.4%) were pathological. The most frequently diagnosed conditions prior to SGU-detected pathologies were pSS (9.7%), rheumatoid arthritis (RA) (13.1%), and systemic lupus (4.6%). One hundred and two patients (57%) had no previous diagnosis (sicca syndrome work-up); of these, 47 patients (46.1%) were ANA positive and 25 (24.5%) anti-SSA positive. In this study, the sensitivity and specificity of SGU for SS diagnosis were 48% and 98% respectively, with a positive predictive value of 95%. There were statistically significant relationships between a pathological SGU and the presence of recurrent parotitis (p=.0083), positive anti-SSB antibodies (p=.0083), and a positive sialography (p=.0351). ConclusionsSGU shows high global specificity but low sensitivity for pSS diagnosis in routine care. Pathological SGU findings are associated with positive autoantibodies (ANA and anti-SSB) and recurrent parotitis.

E022 Effect of upadacitinib in a patient with primary Sjogren syndrome: a case report

Abstract Background/Aims Primary Sjogren syndrome (pSS) is a chronic autoimmune multi-system disease characterized by inflammation of exocrine glands, particularly the lacrimal and salivary glands, as well as multiple extra-glandular involvements. Treatment is often challenging, and until now, no disease-modifying anti-rheumatic drugs (DMARDs) have been approved for this condition. There is a lack of data about the efficacy of Janus kinase inhibitors in pSS. Here we report a patient with pSS successfully responding to upadacitinib. Methods A 68-year-old woman presented with pain in multiple joints for 16 years with intermittent use of NSAIDs. She had no low back pain and no self or family history of psoriasis or red eye. She denied dry mouth but required frequent water drinking during meals to aid swallowing and occasionally used artificial tears. MTX was started for her two-month articular flare and positive rheumatoid factor (RF). MTX caused severe vomiting and hyponatremia, and she was hospitalized. After the correction of hyponatremia, she was put on tofacitinib. We reevaluated the case when she came to us. She had grade 2-3 tenderness of most peripheral joints and was bedridden. Immunological parameters revealed RF 127 IU/ml (reference value &amp;lt;14), anti SSA antibody 147 U/ml (normal &amp;lt;3.2), anti SSB antibody 149 U/ml (reference value &amp;lt;8) and anti CCP antibody; ANA, anti-ds-DNA Ab were negative. There was no erosion on the X-ray hands. Schirmer's test was positive (3 mm bilaterally). Unstimulated salivary flow after five minutes was 0.04 ml/min (≤0.1 ml/min indicates salivary hypofunction). She fulfilled the 2016 ACR/EULAR classification criteria, and we diagnosed her with primary Sjogren syndrome. Hydroxychloroquine was initiated, but she discontinued it for anorexia. Considering her age, she was switched to upadacitinib, as European Medicines Agency restricted the use of tofacitinib beyond 65 years. Results Her EULAR Sjogren Syndrome's Disease Activity Index (ESSDAI) was six at baseline, indicating moderate disease activity. Her joint pain improved significantly within two months with infrequent use of pilocarpine in the sixth month. Six months after treatment with upadacitinib, ESSDAI came down to 2; the Patient's Global Assessment score was 02 and achieved STAR (Sjogren's Tool for Assessing Response) response 7 (STAR responder if score ≥5). Conclusion To our knowledge, this is the first case report on the efficacy of upadacitinib in pSS. Further high-quality clinical trials are required to confirm the benefit of upadacitinib in pSS. Disclosure M. Momen Majumder: None. S. Haq: None.