Immunoglobulin G4 (IgG4)-related diseases are a heterogenous group of chronic inflammatory systemic disorders characterized by fibrosing inflammation with infiltration of IgG4-positive plasma cells. They can affect nearly any organ system. Typical manifestations include autoimmune pancreatitis, sclerosing cholangitis, lymphadenopathy, retroperitoneal fibrosis, and inflammatory orbitopathy as well as involvement of the salivary and lacrimal glands. Each manifestation may present in isolation or in combination with others. Diagnosis requires careful exclusion of malignant or other inflammatory conditions, as IgG4-related diseases can mimic a wide range of disease entities. A multimodal approach combining laboratory findings, histopathological evaluation and radiological imaging is essential for establishing the diagnosis. A structured diagnostic algorithm and close interdisciplinary collaboration are crucial to avoid misdiagnosis and enable appropriate treatment.

BackgroundSjögren’s disease (SjD) is a systemic autoimmune disease that primarily affects exocrine glands. It can be associated with a variety of systemic manifestations, including myositis. At present, data evaluating muscular inflammation in SjD is limited, and further investigation is required.MethodsPatients with SjD and European Alliance of Associations for Rheumatology (EULAR) Sjögren’s syndrome disease activity index (ESSDAI) muscular involvement (EMI) of at least six points in the muscular domain were recruited retrospectively from Hannover Medical School’s SjD cohort after muscular inflammation was ascertained. Patients with SjD and EMI were characterised and compared with age- and sex-matched controls and with the entire SjD cohort.ResultsA total of 26 of 492 SjD patients (5%) were diagnosed with EMI. The mean age of EMI onset was 56.4 years, the ratio between males and females was 12:14. Compared to SjD patients without EMI, SjD patients with EMI showed higher frequencies of Sjögren’s Syndrome-related Antigen A/Ro(52) [SSA/Ro(52)] antibodies (p < 0.001) and elevated levels of immunoglobulin G (p = 0.022). Additionally, ESSDAI scores at initial diagnosis (p < 0.001) and during follow-up (p = 0.003), and the number of immunosuppressive drugs taken over the course of treatment (p < 0.001), were significantly higher in SjD patients with EMI compared to those without muscular inflammation, as shown in the matched analysis, corroborated by the unmatched comparison.ConclusionEMI is a rare but severe manifestation of SjD, occurring simultaneously with sicca symptoms. Male sex, positive SSA/Ro(52) antibodies, and high disease activity are more common in SjD patients with inflammatory myositis compared to those without muscular involvement.

Abstract Background Homozygous or compound heterozygous variants in RNU4ATAC, which transcribes a non-coding RNA component of the minor spliceosome, have been associated with a spectrum of disorders, collectively known as RNU4ATAC-related spliceosomeopathies. The phenotypic spectrum of RNU4ATAC-related disease is characterized by dysmorphic features, growth delay, neurological and skeletal features, whose severity ranges from the microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1) to the milder Roifman syndrome. Objectives To characterize the clinical spectrum and evaluate long-term outcomes of RNU4ATAC-related diseases. Methods We evaluated the phenotypic features of four novel patients with deleterious RNU4ATAC variants, diagnosed by means of whole genome sequencing. Same features were evaluated in previously published cases, identified by literature research on PubMed. Results We identified four novel cases with deleterious compound heterozygous variants in RNU4ATAC, which were not restricted to the 5’ stem-loop, including three adult patients. Reported cases expand the clinical spectrum of RNU4ATAC-related disorders, highlighting renal disease, autoimmunity and systemic inflammation as possibly more frequent yet previously under-recognized features. Immunological investigations reveal enhanced HLA-DR and PD-1 expression in T cells from tested patients, suggesting T cell activation and exhaustion. Reevaluation of all previously published cases confirms the strong correlation of RNU4ATAC variants located exclusively at the 5’ stem-loop with severe lethal disease falling under MOPD1. Genotypes carrying at least one variant that spares the 5′ stem-loop are associated with a milder phenotype and later onset. Conclusion Homozygous or compound heterozygous RNU4ATAC variants affecting the 5’ stem-loop region are associated with severe phenotypes and adverse disease courses. In contrast, genotypes sparing the critical 5′ stem-loop region of RNU4ATAC can cause a complex phenotype that is not necessarily dominated by dysmorphic features or growth failure, but rather by immunodeficiency and immune dysregulation.

Autoantibodies against Ro52 are not only detected in Sjögren’s disease (SjD), but also in idiopathic inflammatory myopathies, where they correlate with the incidence and severity of interstitial lung disease (ILD). It is still unclear whether antibodies against Ro52 are associated with further clinical manifestations in idiopathic inflammatory myopathies, as reduced tear and saliva production as a sign of associated SjD. Thus, this study aimed to determine the prevalence of objective SjD signs in Ro52-positive patients with idiopathic inflammatory myopathies, as well as the prevalence, characteristics, and clinical associations of ILD. A retrospective data analysis of patients from the Departments for Rheumatology, Nephrology, Neurology and Respiratory Medicine at Hannover Medical School, Germany was performed, in which a myositis immunoblot was determined between 2018 and 2024. Out of these patients, a total of 97 patients who were diagnosed with idiopathic inflammatory myopathy were included in the analysis. Overall, antibodies against Ro52 were detected in the myositis immunoblot in 46 of 97 patients (47%), whereas SSA antibodies were only detectable in 37 of 91 patients (41%) in the ELISA test. The detection of anti-Ro52 antibodies was associated with ILD (OR 3.5; p = 0.004). In addition, the presence of anti-Ro52 antibodies correlated with objective sicca symptoms, detected by reduced saliva and/or tear production in the Saxon or Schirmer test (OR 6.3; p=0.026). This study revealed in patients with idiopathic inflammatory myopathies, anti-Ro52 antibodies are associated both with the occurrence of interstitial lung disease and with reduced saliva and tear production. Thus, they mark associated SjD in idiopathic inflammatory myopathy patients.

Die Sjögren-Erkrankung ist eine systemische Autoimmunerkrankung, deren klinisches Spektrum über die klassische Sicca-Symptomatik hinausgeht. Extraglanduläre Manifestationen, insbesondere neurologische Beteiligungen, sind häufig und prognoserelevant. Die neurologischen Manifestationen können das periphere und zentrale Nervensystem betreffen und reichen von Small-fiber-Neuropathien über axonale oder demyelinisierende Polyneuropathien bis hin zu Myelitiden und vaskulitischen Veränderungen des ZNS. Klinisch stehen häufig progrediente sensomotorische Defizite mit Behinderung, Gangstörungen, neuropathische Schmerzen sowie Hirnnervenbeteiligungen im Vordergrund. Die Diagnostik erfordert ein interdisziplinäres Vorgehen. Neben Anamnese und neurologischer Untersuchung sind elektrophysiologische Verfahren, Liquoranalyse, MRT-Diagnostik sowie bei Verdacht auf Small-fiber-Neuropathie eine Hautbiopsie entscheidend. Differenzialdiagnostisch ist insbesondere die Abgrenzung zur chronisch-inflammatorisch demyelinisierenden Polyneuropathie sowie zu metabolischen, toxischen oder hereditären Neuropathien relevant. Klinische Red Flags bei Patienten mit Polyneuropathien, wie Sensibilitätsstörungen nicht nur an den Füßen, sondern auch an den Händen, progrediente motorische Beteiligung mit Lähmungen sowie Hirnnervenaffektionen, sollten an ein Neuro-Sjögren denken lassen. Therapeutisch ist eine phänotyporientierte Strategie erforderlich. Schmerzhafte Small-fiber-Neuropathien werden häufig zunächst symptomatisch behandelt, können jedoch ebenfalls immunmodulatorische Therapien erfordern. Bei progredienten sensomotorischen Neuropathien oder Manifestationen des zentralen Nervensystems sollte frühzeitig eine immunmodulatorische Therapie erwogen werden. Eine enge Zusammenarbeit zwischen Rheumatologie und Neurologie ist essenziell, um die Prognose und den funktionellen Verlauf günstig zu beeinflussen.

ObjectiveCD3γ deficiency is an ultrarare autosomal recessive inborn error of immunity characterized by immune dysregulation and variable immunodeficiency. To date, only 16 predominantly pediatric cases have been reported. Here, we describe two additional adult patients with CD3γ deficiency and provide a comprehensive reevaluation of all previously published cases.MethodsClinical, immunological, and genetic investigations were performed in two adult patients presenting with immune dysregulation and hypogammaglobulinemia. Whole-genome sequencing was used to identify pathogenic CD3G variants, and protein expression was assessed by Western blot analysis. In addition, a literature review of all previously reported cases was conducted.ResultsBoth patients presented with humoral immunodeficiency and Evans syndrome responsive to rituximab therapy. One patient, currently the oldest reported individual with CD3γ deficiency, harbored a novel homozygous frameshift variant in CD3G (c.213dupA, p.(Trp72Metfs*6)) resulting in complete loss of CD3γ expression. Reevaluation of all reported cases demonstrated marked phenotypic heterogeneity, ranging from isolated autoimmune manifestations to severe early-onset combined immunodeficiency requiring hematopoietic stem cell transplantation. Notably, patients carrying identical deleterious variants exhibited substantial variability in clinical presentation and outcomes, indicating that no obvious genotype-phenotype correlation could be established based on the currently available data.ConclusionCD3γ deficiency exhibits a broad and highly variable clinical spectrum extending into adulthood. Immune dysregulation, particularly autoimmune cytopenias, represents a prominent manifestation. Our findings expand the phenotypic spectrum of CD3γ deficiency and emphasize the importance of considering this disorder also in adult patients with hypogammaglobulinemia and autoimmune disease.

Immunglobulin-G4(IgG4)-assoziierte Erkrankungen stellen eine Gruppe chronisch-entzündlicher Systemerkrankungen dar, die durch eine fibrosierende Entzündung mit Infiltration IgG4-positiver Plasmazellen gekennzeichnet sind. Sie können nahezu jedes Organ betreffen; typische Krankheitsmanifestationen sind eine Autoimmunpankreatitis, sklerosierende Cholangitis, Lymphadenopathie, retroperitoneale Fibrose, entzündliche Orbitopathie sowie Beteiligungen der Speichel- und Tränendrüsen. Jede Manifestation kann isoliert oder gemeinsam mit anderen auftreten. Die Diagnostik erfordert den sorgfältigen Ausschluss maligner oder anderer entzündlicher Bedingungen, da IgGA-assoziierte Erkrankungen ein breites Spektrum an Krankheitsentitäten nachahmen können. Bei der Diagnosestellung werden eine Kombination aus klinischen Manifestationen, Laborbefunden und der Histologie sowie auch radiologische Befunde berücksichtigt. Ein strukturierter diagnostischer Algorithmus sowie eine enge interdisziplinäre Zusammenarbeit sind essenziell, um Fehldiagnosen zu vermeiden und eine adäquate Therapie zu ermöglichen.

Filgotinib is an oral Janus kinase 1 (JAK1) preferential inhibitor approved for adult patients with moderate-to-severe active rheumatoid arthritis (RA) who have responded inadequately to, or who are intolerant of, one or more disease-modifying antirheumatic drugs (DMARDs). While randomised trials have demonstrated its efficacy and tolerability, real-world data on very early treatment effects—particularly on pain relief, fatigue and function—remain scarce. The FIRST-RA study was initiated to address this evidence gap under routine care conditions. FIRST-RA is a prospective, multicentre, non-interventional cohort study in Germany and Austria. Approximately 300 adult patients with RA newly starting filgotinib are enrolled and followed for 24 weeks. Patients are stratified into three groups based on prior use of advanced therapies (AT; biologic [b]DMARDs or targeted synthetic [ts]DMARDs): AT-naïve, one prior AT and ≥ 2 prior ATs. Clinical assessments are conducted at baseline and weeks 4, 12 and 24. Patient-reported outcomes (PROs), including the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire, are captured electronically or on paper— daily during week 1 and at regular intervals thereafter. The primary endpoint is the change in RAID pain score from baseline to week 4 (or earlier). Secondary endpoints include fatigue, disease activity, morning stiffness, treatment satisfaction and tolerability. Additional analyses will investigate very early symptom changes, drug utilisation patterns and treatment persistence, as well as effectiveness within AT exposure subgroups (AT-naïve and AT-experienced), summarised descriptively without formal subgroup testing. An exploratory, descriptive analysis will examine how the 2023 label update for JAK inhibitors may have influenced patient characteristics, prescribing patterns and safety outcomes, using the earlier-enrolled FILOSOPHY real-world cohort as an external reference. FIRST-RA is the first real-world study to capture very early symptomatic responses to filgotinib. By integrating PRO data with clinical outcomes, the study aims to support personalised RA management and clarify the use of filgotinib in today’s clinical practice. German Clinical Trials Register, DRKS0003613.

Background:Rare inflammatory rheumatic diseases are often characterized by heterogeneous, multisystemic symptom patterns, complicating early diagnostic differentiation. This study aimed to model a structured, symptom- and laboratory-based decision approach for risk stratification of rheumatologic diagnoses in patients referred to a tertiary Center for Rare Diseases (CRD) with unclear systemic complaints. Methods:We conducted a retrospective cross-sectional analysis of 173 patients evaluated at a CRD. Patients were classified into rheumatologic (RHEUMA) and non-rheumatologic (OTHER) diagnostic groups based on final diagnostic outcomes. A standardized questionnaire capturing 52 symptoms was aggregated into domain-specific and composite scores. Laboratory data were summarized into predefined indices. Group differences were analyzed descriptively using inferential statistics. A decision tree model based on Chi-Square Automatic Interaction Detection (CHAID) was constructed to support structured risk stratification. Results:A confirmed rheumatologic diagnosis was established in 52.0% of patients. Symptom and comorbidity patterns were broadly similar across diagnostic groups, with fatigue and generalized pain being the most prevalent complaints. The RHEUMA group showed significantly higher scores in selected symptom domains and in an immunoserological laboratory index (all p < 0.05). The CHAID-based decision model, integrating symptom scores, laboratory markers, and autoimmune history, showed an apparent classification of 81.5% (AUC = 0.893), compared to 76.3% (AUC = 0.823) for logistic regression. Conclusion:The proposed decision tree model provides a transparent framework for structured risk stratification in a highly preselected tertiary referral population. Given the monocentric, retrospective, and exploratory study design, the findings should be interpreted as hypothesis-generating. External validation in independent cohorts is required to assess model generalizability, calibration, and robustness before clinical implementation can be considered. Within these constraints, the approach illustrates the potential of transparent, rule-based symptom aggregation to support structured clinical reasoning and prioritization in complex multisystem presentations.

INTRODUCTION:Sex-related differences in interstitial lung disease (ILD) phenotypes are well recognized, but it remains unclear whether sex itself independently influences outcomes in non-idiopathic pulmonary fibrosis (non-IPF) ILD once comorbidities, lung function, and treatment are considered. METHODS:In the prospective INSIGHTS-ILD registry (data cut 17 September 2025), we compared men and women with non-IPF ILD using descriptive analyses and Cox models with prespecified adjustment steps: model A (age, comorbidity count, and smoking), model B (A + forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide [DLCO]), and model C (B + antifibrotic therapy). Prespecified subgroup analyses included age strata (≤55 and >55 years) and ILD entities. Longitudinal FVC and DLCO trajectories were assessed over 24 months. RESULTS:Among 883 patients (483 men and 400 women), exposures and disease entities differed significantly by sex: men reported more occupational/environmental exposures and had higher rates of fibrotic idiopathic interstitial pneumonia, whereas women more frequently had autoimmune-related ILD and a family history of ILD. Men had a higher comorbidity burden and more often received antifibrotic therapy at baseline. Survival was shorter in men (HR: 1.51; 95% CI: 1.03-2.21), but this association disappeared after adjustment in model A (HR: 1.04; 95% CI: 0.65-1.68), model B (HR: 1.03; 95% CI: 0.61-1.74), and model C (HR: 1.04; 95% CI: 0.62-1.77). Progression-free survival and transplant-free survival showed no consistent sex-related differences. Longitudinal FVC and DLCO declines were modest and largely parallel in both sexes, with no significant between-group differences. Findings were similar across age groups and ILD entities. CONCLUSION:Men and women with non-IPF ILD differ in exposures, phenotypes, and comorbidities, but after accounting for these factors, sex is not an independent predictor of survival or functional progression. Risk assessment should therefore primarily be based on objective disease characteristics rather than sex alone.

Objectives Treatment of rheumatoid arthritis (RA) relies on immunomodulatory drugs that can compromise immunity, inducing secondary immunodeficiency (SID). However, features of SID, such as hypogammaglobulinaemia and severe/recurrent infections, occur in only a minority of patients, suggesting a potential underlying genetic predisposition. Given the expanding spectrum of genes implicated in inborn errors of immunity (IEIs) and the fact that IEIs can present with rheumatic manifestations, we hypothesised that a subset of patients with RA with SID harbour IEI-related variants.Methods We screened 701 patients with RA for SID, defined as persistent hypogammaglobulinaemia or susceptibility to infections requiring prophylactic anti-infective therapy. Patients with SID underwent targeted whole-exome sequencing to identify rare variants in IEI-associated genes.Results Among 701 evaluated patients, 70 (10%) had SID. SID was more frequently observed in patients with earlier onset of RA, seronegative disease and in those receiving rituximab therapy. Genetic analysis identified 17 putatively pathogenic variants in 15 of 70 patients with SID (21.4%). All variants were monoallelic, with 7 of 17 (41.2%) affecting genes involved in canonical NF-κB signalling. Two patients (3.1%) harboured variants previously reported as pathogenic.Conclusions Although rare, underlying IEIs can account for immunodeficiency in patients with RA. Identifying patients with IEIs among those with RA may have important implications for disease management, as it can guide the selection of immunomodulatory therapy and help prevent infectious complications. Furthermore, it may refine our interpretation of drug safety, particularly in cases of unusual infections that may instead be attributable, rather, to an underlying germline defect.

Background: Psoriatic arthritis (PsA) often requires escalation from conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to biologic therapy (bDMARDs), yet biomarkers guiding treatment decisions remain limited. Anti-CD74 autoantibodies have shown diagnostic potential in axial spondyloarthritis, but their relevance in PsA is insufficiently characterized. Objective: To evaluate whether IgA anti-CD74 levels are associated with treatment escalation in peripheral PsA (pPsA) and to characterize their relationships with clinical and immunological parameters. Methods: Serum samples from 171 PsA (127 pPsA, 44 axial PsA [axPsA]), 43 non-rheumatic disease controls (NRD), and 43 rheumatoid arthritis (RA) patients were analyzed. IgA anti-CD74 levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients were stratified by disease duration and treatment exposure. Correlation analyses, receiver operating characteristic (ROC) curves, and logistic regression models were performed. A prospective subgroup of 53 early pPsA patients was followed to assess treatment initiation. Results: IgA anti-CD74 levels were elevated in PsA compared with NRD controls (median 13 vs. 6 U/mL, p < 0.0001), with similar levels in pPsA and axPsA and comparable values in RA, indicating an association with inflammatory disease rather than disease specificity. Anti-CD74 positivity (>15 U/mL) was observed in 31.5% of pPsA and 43.2% of axPsA versus 2.3% of NRD, independent of disease duration. Anti-CD74 levels were associated with treatment escalation in pPsA, with higher levels in bDMARD-treated patients (median 13.0 vs. 11.0 U/mL, p = 0.04). In multivariate analyses, anti-CD74 was independently associated with csDMARD (OR 1.113, p = 0.022) and bDMARD use (OR 1.052, p = 0.02). After false discovery rate (FDR) correction, anti-CD74 remained associated with serum IgA (q = 0.0008) and weakly with IgG (q = 0.0250), but not with C-reactive protein (CRP) or age. Longitudinal associations were not significant after FDR correction (csDMARD initiation: p = 0.047, q = 0.094; bDMARD initiation: p = 0.19, q = 0.1866), indicating these findings are exploratory. Conclusion: IgA anti-CD74 levels are elevated in PsA and appear to reflect immunological activity not captured by CRP. Their independent association with treatment escalation in pPsA supports further evaluation as a biomarker candidate, although findings remain exploratory and require validation in larger longitudinal cohorts.

BACKGROUND:Insufficient access to specialist rheumatology services in Germany results in prolonged waiting times and delayed diagnostic confirmation, which impedes timely and effective initiation of therapy. OBJECTIVES:This study examines the impact of early versus delayed access to specialist care on medication prescribing patterns and associated costs. MATERIALS AND METHODS:A cost analysis was conducted within the Deliver-Care study using health insurance claims data from 2015-2020. Patients with a confirmed rheumatoid arthritis diagnosis (ICD-10 M05/M06) were stratified by the timing of their initial specialist consultation: early access (within the diagnosis quarter, Q1) versus late access (Q2-Q4). Medication costs were compared across these groups. RESULTS:More than half (57.4%) of M05 patients and about one quarter (24.4%) of M06 patients had no access to a specialist during the first year after the initial suspected diagnosis. Among patients who did have specialist contact (n = 3781), 82.7% obtained early specialist access. Patients with delayed specialist access incurred higher medication costs (€ 4343 in Q4 vs. € 1763 in Q1; p < 0.0001). A sensitivity analysis showed that patients with delayed specialist access were switched to high-cost medications earlier than those with early access. CONCLUSION:Early specialist access is associated with reduced biologic prescribing and lower medication costs. These findings highlight that timely diagnosis and treatment not only lessen patient disease burden but also generate substantial cost savings in the management of rheumatoid arthritis.

Spondyloarthritis (SpA) is a set of immune-inflammatory conditions characterized by musculoskeletal and extra-articular manifestations. Increasing evidence indicates that alterations in the gut microbiota (dysbiosis) may influence both mucosal and systemic immune responses, potentially contributing to the loss of tolerance and the development of autoantibodies in SpA. This narrative review examines the current evidence linking gut dysbiosis to autoantibody development in SpA, with particular focus on ankylosing spondylitis (AS) and psoriatic arthritis (PsA). We summarized key mechanistic pathways, including Th17 axis activation, molecular mimicry, increased intestinal permeability (“leaky gut”), and altered microbial metabolite signaling. We discussed the potential relevance of these mechanisms to SpA-associated autoantibodies such as anti-CD74, anti-HSP65, and anti-Kaiso. Where direct evidence in SpA is limited, findings from other autoimmune diseases are considered as mechanistic analogies rather than definitive parallels. We further review microbiome-targeted therapeutic strategies, including probiotics, prebiotics, and bacterially based therapies, and highlight differences between preclinical findings and available clinical data. Although biologically plausible mechanisms, direct causal evidence linking gut dysbiosis to autoantibody production in SpA remains limited, and clear methodological heterogeneity persists across microbiome studies. Overall, while modulation of the gut-immune axis represents a promising research direction in SpA, further mechanistic and longitudinal human studies are required before microbiota-targeted interventions can be considered applicable for autoantibody modulation.

ABSTRACT Objective The Brief-cope questionnaire explore coping behavior. However, the underlying factor structure remains a subject of ongoing debate. Exploratory factor analyses (EFA) conducted across different populations have identified factor solutions ranging from two to fourteen factors. As of yet, the underlying factor structure of the Brief-cope has not been investigated in patients with seropositive rheumatoid arthritis (RA). Therefore, the aim of this study was to explore the underlying factor structure of the Brief-cope in a German population of seropositive RA. Methods 216 outpatients with seropositive RA completed the Brief-cope. An EFA with principal axis factoring and Promax rotation was conducted. Results EFA indicated a five-factor solution. The five-factor solution explained 51.95% of variance. The identified factors were: (1) problem-focused coping (Cronbach’s α = .851), (2) emotion-focused coping ( α = .754), (3) maladaptive coping ( α = .747), (4) religious coping ( α = .851), and (5) substance-use coping ( α = .869). Conclusion A five-factor solution provided the most appropriate representation of the underlying factor structure of the Brief-cope in patients with seropositive RA. This factor structure may serve as a suitable basis for future analyses of Brief-cope data in comparable RA populations. Trial registration number DRKS00013055.

Eosinophils are key factors to the pathogenesis of severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis (EGPA). Monoclonal antibodies targeting the interleukin-5 (IL-5) pathway (mepolizumab and benralizumab) often lead to rapid symptom control and enable tapering of oral corticosteroids (OCS) in many patients. We present the case of a 51-year-old male patient with severe eosinophilic asthma, peripheral blood eosinophilia, and ear, nose, and throat (ENT) involvement, treated with benralizumab (30 mg every 8 weeks) and oral corticosteroids. During tapering of corticosteroids, the patient developed diffuse alveolar haemorrhage as a manifestation of overt vasculitis. Subsequently, elevated troponin T levels were detected, and further diagnostic work-up revealed both myocardial involvement consistent with EGPA and an acute myocardial infarction due to occlusion of the left anterior descending (LAD) artery. Central immunopathogenic pathways involved in vasculitis are not targeted by IL-5 antibodies and vasculitic manifestations may relapse or even newly emerge despite ongoing biological therapy. Elevated troponin levels in EGPA patients should only be attributed to EGPA once other potential causes of myocardial injury are ruled out.

Primary Sjögren’s disease (SjD) is a systemic autoimmune disorder where diagnosis relies on the presence of Ro/SS-A and La/SS-B autoantibodies. However, approximately one-third of SjD patients are seronegative, often requiring an invasive minor salivary gland biopsy, which can lead to significant diagnostic delays. This review comprehensively evaluates a wide array of novel autoantibodies to determine their potential as diagnostic biomarkers for Ro/SS-A-negative SjD patients. While many newly identified autoantibodies, such as those targeting ASCA, TRIM38, and PUF60, were found to be strongly associated with Ro/SS-A positivity and thus offer limited utility for seronegative diagnosis, several others show significant promise.Notably, autoantibodies targeting functional proteins like the muscarinic M3 receptor (anti-M3R) have demonstrated high diagnostic sensitivity and specificity. Furthermore, systematic screenings have uncovered highly specific markers. One panel of 12 autoantigens (including GMNN, GRAMD1A, and NUP50) identified by human proteome arrays exhibited 54% sensitivity with 100% specificity for Ro/SS-A-negative SjD. Another validated panel combining immunoglobulin G autoantibodies against FNBP4, SNRPC, CCL4, M3R, and KDM6B achieved 46% sensitivity with 95% specificity. Other individual markers, such as anti-NA14 and anti-calponin-3, also show potential for identifying seronegative SjD subsets.In conclusion, a growing body of evidence supports the clinical utility of several novel autoantibodies in diagnosing Ro/SS-A-negative SjD. The integration of these biomarkers into clinical practice could significantly improve early and accurate diagnosis, reduce the reliance on invasive procedures, and potentially aid in patient stratification for targeted therapies. Further validation of these markers in large cohorts is warranted.