Amita Aggarwal

Background The presence of hip arthritis in spondyloarthropathies (SpA) suggests a severe disease. Data on comparative burden, outcome, and associated factors of hip involvement in juvenile and adult SpA is limited. Methods This was a cross-sectional, observational study involving patients with enthesitis-related arthritis (ERA) (n = 513) and adult SpA (n = 504) attending a tertiary-care rheumatology department. Clinical data including demographics, musculoskeletal involvement, HLA-B27 status, medication use, and (total hip replacement) THR were recorded. Data were analyzed using descriptive statistics and multivariate logistic regression models. Result ERA patients had longer disease duration at last visit (median 9 vs 6.5 years). Hip arthritis prevalence was higher in ERA than adult SpA (29.2% vs 18.5%; p < 0.001). In pooled multivariable analysis (n = 703), ERA (adjusted OR 1.97, 95% CI 1.37–2.83; p = 0.001), longer disease duration (OR per year 1.04, 1.02–1.06; p = 0.001), and sacroiliitis (OR 2.49, 1.47–4.23; p = 0.001) were independently associated with hip arthritis. Sacroiliitis grade had a direct relationship with prevalence of hip arthritis, each one grade increased odds of hip arthritis by 73% (adjusted OR 1.73, 1.29–2.31; p < 0.001). THR was performed in 4.5% ERA and 2.6% SpA patients. Only disease duration was independently associated with THR (adjusted OR per year 1.07, 1.03–1.11; p = 0.003). Conclusion Hip arthritis was more common in ERA than adult SpA even after adjustment for disease duration. Disease duration was independently associated with total hip replacement in patients with hip arthritis. Key Points • Hip arthritis is more common in ERA than in adult SpA and is more often bilateral. • Grade of sacroiliitis and disease duration have dose response relationship with development of hip arthritis in both ERA and adult SpA. • Longer disease duration is associated with the need for total hip replacement in spondyloarthritis.

Autoinflammatory disorders (AIDs) are a clinically heterogeneous group of inborn errors of immunity primarily caused by dysregulation in the innate immune system. Clinical diagnosis is often challenging due to clinical heterogeneity and the overlapping phenotypes with other inborn errors of immunity and monogenic conditions that mimic AIDs. Worldwide, and especially in India, there is a lack of systematic large cohort studies employing genomic testing early in the course of evaluation for individuals with autoinflammatory disease. Herein, we describe our experience using exome sequencing as a first‐tier investigation in evaluating 202 individuals from 196 unrelated families with possible monogenic AIDs. Consanguinity was noted in 19% of the families. Recurrent fever was the most common manifestation (90%), frequently associated with arthritis (54%), skin lesions (38%), hepatosplenomegaly (23%), oral ulcers (21%) and lymphadenopathy (21%). Exome sequencing could identify a molecular diagnosis in 50 of 196 (25%) families of whom 30 (60%) had variants in genes associated with monogenic AIDs, 10 (20%) had other distinct inborn errors of immunity and 10 (20%) had monogenic conditions with phenotypic overlap with AIDs. We identified 21 variants in genes associated with monogenic AIDs, of which 20 (95%) were single nucleotide variants and one (5%) was a copy number variant. Notably, seven (33%) of the 21 variants were novel. This study highlights the diagnostic challenges posed by phenotypic overlap in this group of disorders and demonstrates the utility of exome sequencing in enabling a timely diagnosis, including conditions that mimic AIDs thereby facilitating targeted therapy and genetic counseling.

Objective: To evaluate longitudinal antiphospholipid antibody (aPL) patterns in newly diagnosed systemic lupus erythematosus (SLE) and their association with vascular events, disease activity and organ damage. Methods: We conducted a prospective study within the INSPIRE registry including patients with newly diagnosed SLE (median disease duration 232 days [114–484]) with serum at baseline, 6 and 24 months. Anti-cardiolipin (aCL) and anti-β2-glycoprotein I (anti-β2GPI) IgG/IgM were measured by ELISA, and lupus anticoagulant when feasible. aPL positivity was analysed using manufacturer cut-offs and moderate–high titres (>40 U). Patients were classified as persistently negative, positive, fluctuating or negativized. High- and low-risk aPL profiles were defined per EULAR recommendations. Associations with thrombosis, SLEDAI-2K, Physician Global Assessment (PGA) and SLICC/ACR Damage Index (SDI) were assessed. Results: Among 270 patients, 77.1% were aPL positive at least once, predominantly low-titre. Moderate–high titre aPLs were less frequent and stable. Most patients with baseline negativity or low-titre/single positivity reverted to negative, whereas dual or triple positivity was associated with persistence. A subgroup (3.1%) progressed from negative/low-titre to high-risk profiles. aPL negativization occurred in 12.5% and was inversely associated with baseline aPL burden. Over 2 years, 19 (7%) developed thrombosis, with higher risk in high-risk and persistently positive groups; no thrombotic events occurred in persistently aPL-negative patients. aPL titres did not correlate with SLEDAI-2K or PGA, while aCL IgG and anti-β2GPI IgG correlated weakly with anti-dsDNA. SDI remained low across groups. Conclusion: In early SLE, aPLs are largely low-titre and fluctuating, with some patients evolving to higher-risk states, supporting serial aPL testing.

Myositis specific antibodies are clinically useful biomarkers in inflammatory myositis. Although immunoprecipitation is regarded as the gold standard, line immune assay (LIA) is widely used in practice. However, LIA is limited by multiple MSA positivity in up to 15% of patients, which limits its applicability in diagnosis and prognostication. We sought to interrogate the subset of patients with multiple antibody positivity on LIA to determine a new positive control band index with high specificity for the diagnosis of myositis. We retrospectively reviewed all samples tested for MSA (EUROLINE DL 1530-1601-4G) between April 2023 to April 2025. We calculated the PCBI (test reading/positive control) and compared it with optimal cutoffs as per EUROLINE and how it impacted multiple antibody positivity. Diagnosis of myositis subtype was confirmed by 2 rheumatologists. We retrieved records of 235 patients, 59.6% females with a mean age of 46.1 years. The underlying diagnosis was dermatomyositis (8.5%), juvenile dermatomyositis (2.1%), anti-synthetase syndrome (7.7%), necrotizing myopathy (2.6%), malignancy associated (4, 1.7%), MSA negative IIM or polymyositis (8, 3.4%) and CTD associated myositis (12, 5.1%) and ILD for IPAF evaluation (139, 59.1%). Multiple MSA positivity was seen in 25 patients (10.6%) with EuroLine, Using the revised PCBI cutoffs, we could discriminate between 14 of these MSA’s and 11 remained positive for multiple antibodies. On correspondence analysis, both Euroline cutoffs and PCBI showed association between antibody positivity and clinical diagnosis (Chisq p values < 0.001). However, using the PCBI, 73.4% of the variability in the data compared to 69.13% with Euroline cutoffs. Rather than a single uniform cut off for all patients, a phenotype specific cut off for each clinical phenotype at the time of clinical assessment might offer a higher specificity for MSA with line immune assay.

Background HLA-B27 is a susceptibility factor for enthesitis-related arthritis. HLA-B27 transgenic rats do not develop disease in a germ-free state, suggesting involvement of the gut in the pathogenesis of the disease. There is limited data on the effect of HLA-B27 carriage and gut flora in JIA-ERA. Methods Stool samples from 10 HLA-B27-positive and 5 HLA-B27-negative JIA-ERA patients, and 10 HLA-B27-negative healthy controls were collected after consent. Fecal calprotectin and serum LPS levels were measured using ELISA. The fecal flora was assessed using 16S rRNA based sequencing. Results HLA-B27-positive patients had higher fecal calprotectin levels (p < 0.001) compared to HLA-B27-negative patients and HC. However, serum LPS levels were not different. Alpha and beta diversity of fecal flora were similar in HLA-B27-positive and negative patients, but different compared to HC. HLA-B27-positive patients had higher abundance of family Veillonellaceae, Prevotellaceae and genera Moryella, Intestinimonas, Fournierella, Leyella, Massiliprevotella, Segatella, and Bilophila and lower abundance of genera Bifidobacterium compared to HC. At the species level, the abundance of Coprococcus eutactus and Prevotella copri was higher while that of Dorea longicatena was lower in HLA-B27-positive patients compared to HC. In addition, there was lower abundance of the genera Fusicatenibacter and Lachnospiraceae NC2004 group, species belonging to genera Agathobacter, Fusicatenibacter, Butyricicoccus, and Acutalibacter and higher abundance of genera Leyella in HLA-B27-positive patients compared to HLA-B27-negative patients. Conclusion Lower abundance of anti-inflammatory and higher abundance of pro-inflammatory bacteria in HLA-B27-positive JIA-ERA patients by inducing gut inflammation may play a role in disease pathogenesis. Key Points • The presence of HLA-B27 in JIA-ERA patients is associated with a decline in the population of beneficial bacteria with anti-inflammatory properties and an increase in gut inflammation. • Exploration of supplementation with butyrate or SCFA to improve gut health may be beneficial in patients with JIA-ERA.