AIM:To update the Asia-Pacific League of Associations for Rheumatology (APLAR) treatment recommendations for rheumatoid arthritis (RA) by incorporating new evidence and reassessing the validity of previous guidance: METHODS: A literature search for relevant publications from January 2018 to August 2023 was conducted, supplemented by earlier studies where relevant. Recommendations were formulated based on this evidence and refined through a modified-Delphi process during a series of online meetings. The quality of evidence and strength of recommendations were assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS:This update comprises 14 statements that achieved consensus during the meetings. Topics covered include measurement of disease activity and treatment response, the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), the use of targeted therapies, vaccination and screening for infections and the use of DMARDs during pregnancy. The recommendations address the selection of disease activity scores, initiation and intensification of therapy using csDMARDs and targeted therapies, and management of RA in patients at risk of reactivation of infectious diseases. These recommendations are discussed in the context of the clinical landscape encountered in the Asia-Pacific region. CONCLUSION:These updated recommendations complement previous APLAR guidelines and aim to support best practice management of RA across the Asia-Pacific region. They provide a practical framework for national rheumatology associations to develop local guidelines adapted to their specific needs and clinical practice.

The association between heterozygous C4 deficiency and systemic lupus erythematosus (SLE) is unclear. There is a lack of data in South Asian Indians on any possible association of C4A and C4B null alleles with lupus. We aimed to study the prevalence of C4A and C4B null alleles in a cohort of SLE patients with persistently low C4 levels compared to healthy controls (HC). Patients with SLE and HC were recruited for this prospective observational study. C4 (C4AQ and C4BQ) polymorphisms were tested using a touch-down polymerase chain reaction protocol. One hundred and three SLE patients and 103 HC were included in the study. Persistently low C4 levels were observed in 25 (23.6%) of SLE. The frequency of C4A and C4B null alleles was similarly distributed across SLE and HC (4% and 3.8%, respectively). Univariate analysis showed a low age, higher proportion of elevated dsDNA, and higher positive anti-SSA (Sjogren's syndrome-related antigen A) antibodies at presentation were associated in SLE patients with the null allele group on comparison without the null allele group. However, these associations did not persist in the multivariate analysis. In conclusion, C4 null allele frequency was similar in SLE and HC. No characteristic associations were observed in SLE with C4 null alleles was observed. Therefore, C4 null allele is an unlikely explanation for persistently low C4 in South Indian Asian patients with lupus.

BACKGROUND:The management of patients with Takayasu arteritis (TAK), especially those who are refractory to biologic disease-modifying anti-rheumatic drugs (DMARDs), is challenging. OBJECTIVE:We determined the efficacy of tofacitinib in patients with TAK who could not achieve or maintain stable disease despite biologic DMARDs (bDMARD-NR). METHODS:Details of consecutive patients with TAK treated with originator/generic tofacitinib at 5 centres in India were recorded retrospectively from the medical records. The activity of the disease was assessed using multiple domains including Indian Takayasu arteritis score (ITAS), C-reactive protein (CRP) and imaging. Active disease was defined by either (i) ITAS-A(CRP) ≥ 3 wherein both ITAS and CRP each contributed at least 1 point to the final score; or (ii) clinical ITAS score > 1 in the presence of imaging activity even without raised CRP. The parameters between patients with good response and no response to treatment were compared. RESULTS:Altogether, 33 patients (30 females) with a mean age of 28.9 ± 7.6 years and a disease duration of 39.0 (15.8-72.0) months who received tofacitinib were included. Sixteen patients (54.5%) who failed anti-TNF agents [n = 14, (42.4%)] or tocilizumab [n = 14, (42.4%)] were classified as bDMARD-NR. During a follow-up of 15.0 (6.5-20.0) months, 23 (69.7%) satisfied the above composite criteria for inactive disease using clinical, laboratory, and imaging parameters. Among bDMARD-NR, 14 (77.8%) achieved inactive disease. Four patients discontinued tofacitinib due to adverse drug events. No predictors of response were identified. CONCLUSION:Tofacitinib may be an effective option in a subset of patients who fail to attain stable disease state despite use of csDMARDs and bDMARDs.

BACKGROUND AND OBJECTIVES:Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive Interstitial lung disease (ILD) that has a significant impact on the health-related quality of life (HRQoL). There are generic and disease-specific questionnaires to assess this, but no literature from India exists. HENCE WE DECIDED:to estimate HRQoL and to determine its predictors in a cohort of patients attending a tertiary care centre in Southern India. METHODS:Consecutive consenting patients diagnosed with IPF by the ILD MDD between September 2023 and August 2024 were self-administered the St. George's Respiratory Questionnaire (SGRQ) and the King's Brief Interstitial Lung Disease (KBILD) questionnaire to assess the HRQoL. RESULTS:In all, 70 patients with IPF were recruited into the study. The median total SGRQ was 35.9 (23.9-57.8), and the median total KBILD was 54.5 (46.4-65.6). Based on SGRQ (>30), 63% (44/70) and based on KBILD (≤50), 34% (24/70) had a poor quality of life. The SGRQ was significantly lower in those not on antifibrotics across all domains, with a trend towards near significance in the activity domain. The Gender, Age, Physiology (GAP) Index had a significant association with the KBILD - breathlessness and activity domain (P value = 0.01) and the total score (P value = 0.02). CONCLUSION:This is the first Indian study reporting HRQoL in IPF. IPF impacts HRQoL drastically, with a predominant impact on physical wellness and a lesser effect on psychological well-being. KBILD is associated with the GAP index. A larger study is required to identify independent factors associated with HRQoL.

Aim: The present study is intended to evaluate the factors influencing the diagnostic and rheumatology care referral delay in patients with spondyloarthropathy (SpA) and psoriatic arthritis (PsA) in India. Materials and methods: The independent prospective, multicentre, observational study collected data from 8 centres across India through the database created by the Indian Rheumatology Association (IRA). Modified Prasad scale was used for socio-economic classification based on the patient’s income. The data of PsA and SpA were analysed separately, and the causes were compared using t-test for continuous variables and chi-square and Fisher’s exact tests for categorical variables. Results: The mean referral delay noted for PsA and SpA subjects were 16.3±34.35 and 17.48±33.59 (IQR 24 and 34) months, respectively. Majority of the PsA patients and about 65% of SpA subjects reported a lack of awareness of the rheumatology specialty as the major reason for the delay. Another major reason was management by other specialists instead of rheumatologists (65% and 74% respectively). Approximately 8% of patients in both disease groups had no faith in modern care due to perceived elevated risk of adverse effects. SpA patients with improved socio-economic status had a higher proportion of subjects seeking specialty care. A direct association was noted between professional skill and early access to specialty care for both PsA and SpA patients. Conclusion: The lack of awareness of rheumatology as a specialty and patients being managed by other specialties are the two major reasons for delayed referral of SpA and PsA. Additionally, a patient’s economic and skill level can influence their ability to access specialty care.

Takayasu arteritis (TA) is a chronic granulomatous inflammatory disease affecting the aorta and its branches. Paediatric TA (pTA) may present from 6 months after birth till the adolescent age group. Genetics and pathogenesis of pTA are not fully understood. Earlier studies reported monogenic mutation in NOD2, XIAP, and STAT1 genes in patients with pTA. TA, a relatively rare disease, is more common in geographical pockets, including India. We hypothesized that South Asian patients with pTA, namely, those of Indian subcontinent origin, may have clinically relevant and unique pathogenic variants involving one or more genes, especially those linked to genetically driven vasculitic illnesses, including autoinflammatory pathologies. Children with pTA fulfilling EULAR/PRINTO/PReS classification criteria and presenting with clinical symptoms to the Paediatric Rheumatology clinic of Christian Medical College, Vellore, were included. Blood samples were collected after getting informed consent from parents or guardians and assent forms from children. DNA was extracted from whole blood using the Qiagen DNA extraction kit. Initially, the common variant in Indian population, namely, ADA2 c.139G > A; p.Gly47Arg, was screened, followed by whole exome sequencing. Fourteen children were recruited for the study. Median age of patients was 11 years (4 months–14 years) with a male-to-female ratio of 4:10. Distribution of angiographic subsets by Numano’s classification of included children were as follows: type 5 (n = 7), type 4 (n = 5), and type 3 (n = 2). We identified novel variants in ten different genes. This include variants in genes of classical complement pathway, namely, C2, C3, C6, C7, and C9, and other genes, namely, CYBA, SH3BP2, GUCY2C, CTC1, COL5A1, and NLPR3. Two of 14 patients have heterozygous pathogenic variants; this implies that combination of heterozygous variants in C3 and COL5A1 might lead to disease development, suggesting digenic inheritance. One patient has a homozygous variant in CYBA. None of the patients were identified to have ADA2 variants. Whole exome sequencing reveals combination of rare variants in genes C3, COL5A1, and CYBA associated with disease development in children with Takayasu Arteritis.

Objectives The primary aim of the CHANGE survey is to determine the current state of gender equity within rheumatology, and secondarily, to review the physician perspective on bullying, harassment and equipoise of opportunities within rheumatology.Methods The CHANGE e-survey is a cross-sectional self-reported questionnaire adapted from EULAR's gender equity in academic rheumatology task force. The survey was launched in January 2023; it is available in six languages and distributed widely via rheumatology organizations and social media. Eligible participants include rheumatologist physicians and rheumatology health-care professionals. Survey responses will undergo descriptive analysis and inter-group comparison aiming to explore gender-based discrimination using logistic regression, with subgroup analyses for country/continent variations.Conclusion This e-survey represents a comprehensive global initiative led by an international consortium, aimed at exploring and investigating the gender-related disparities and obstacles encountered by rheumatologists and rheumatology health-care professionals across diverse communities and health-care environments. By pursuing this initiative, we aim to take the broader rheumatology community a step closer to understanding the underlying origins of inequities and their determinants. Such insights are pivotal in identifying viable interventions and strategies to foster gender equity within the field. Ultimately, our collective objective is to ensure equitable access to opportunities for every individual, irrespective of gender, thereby promoting inclusivity and fairness across the entire spectrum of professional practice and career development. What does this mean for patients?The CHANGE Study, led by a team of rheumatology professionals worldwide, is working to make health care more equal for everyone. We are focusing on challenges faced by rheumatologists, such as fair pay and career opportunities. To understand these issues better, the team is gathering information through a global survey of rheumatology professionals. The goal is to find out why there are differences and come up with solutions. Ultimately, the aim is to create a fair and inclusive environment in rheumatology, ensuring that everyone has the same chances to grow in their careers, regardless of their gender. The findings of the study will help to create better guidelines, promoting fairness and equality for health-care professionals in rheumatology.

BACKGROUND:Unilateral presentation of sacroiliitis is a diagnostic dilemma, especially between infection and inflammatory sacroiliitis associated with spondyloarthritis, requiring an early and accurate diagnosis. OBJECTIVE:To assess the utility of magnetic resonance imaging (MRI) in differentiating infective versus inflammatory etiology in unilateral sacroiliitis. MATERIALS AND METHODS:Retrospective review of the MRI of 90 patients with unilateral sacroiliitis, having an established final diagnosis. MR images were evaluated for various bone and soft tissue changes using predefined criteria and analyzed using univariate and multivariate regression analysis. RESULTS:Among the 90 patients, infective etiology was diagnosed in 66 (73.3%) and inflammatory etiology in 24 (26.7%). Large erosions, both iliac and sacral-sided edema, joint space involvement with effusion or synovitis, soft tissue edema, elevated ESR/CRP, and absence of capsulitis and enthesitis were associated with infection (p < .001). The independently differentiating variables favoring infection on multivariate analysis were-both iliac and sacral-sided edema (OR 4.79, 95% CI: 0.96-23.81, p = .05), large erosions (OR 17.96, 95% CI: 2.66-121.02, p = .003), and joint space involvement (OR 9.9, 95% CI: 1.36-72.06, p = .02). Exclusive features of infection were osteomyelitis, sequestra, abscesses, sinus tracts, large erosions, and multifocality. All infective cases had soft tissue edema, joint space involvement, elevated ESR, and no capsulitis. CONCLUSION:MRI evaluation for the presence and pattern of bone and joint space involvement, soft tissue involvement, and careful attention to certain exclusive features will aid in differentiating infectious sacroiliitis from inflammatory sacroiliitis.

AIM:The study aims to identify factors influencing referral patterns and delays in rheumatoid arthritis (RA) patients across clinical settings in India. MATERIALS AND METHODS:A prospective, multicenter, observational study collected data from eight centers using the Indian Rheumatology Association (IRA) database. Patient-related factors and referral factors were determined based on patient narration. The modified PRASAD scale categorized patients' socioeconomic status. RESULTS:The study included 4,643 RA patients from eight centers. Data from 35 patients were excluded due to inconsistent reporting of diagnosis and delay. Lack of awareness was the predominant factor causing the delay in referral. Approximately, 39% of patients were referred to the rheumatology specialty within 6 months of disease onset, while 26% reported later, and 34% reported over 2 years. Referral delays were linked to socioeconomic factors in Madhya Pradesh (21.43%) and West Bengal (28.57%). Lack of awareness about the disease and rheumatology specialty was highest in West Bengal (100%), followed by Delhi and Rajasthan (93.70%). Misconceptions about modern medicine, reluctance to refer patients to the rheumatologist, and previous treatment by other specialities were other factors influencing referral delay. Primary care clinicians' unawareness of the rheumatology specialty was the primary reason for referral delay in Gujarat (33.56%) and Delhi and Rajasthan (25.18%). CONCLUSION:Both patient and healthcare professional-related factors contribute to referral delays in RA patients. Major factors causing referral delays include reluctance to refer and inadequate knowledge about rheumatology among primary care physicians and the general public. Patients' education and occupation also influence the timing of referrals to specialty care.

We performed genetic association study for genes encoding angiogenic and angiostatic proteins in patients with Takayasu arteritis (TAK). A total of 96 SNPs involving 60 genes were studied. Genotyping was performed in Fluidigm 96.96 Dynamic Array chip. All statistical analysis for SNP evaluation was performed using PLINK software. Initial analyses revealed five SNPs from three genes [ IL-18 (encodes Interleukin-18), FGF2 (encodes Fibroblast Growth Factor-2), and ANGPT1 (encodes Angiopoietin-1)] as significantly different between controls and cases (uncorrected p < 0.05). After permutation-based analysis, two tag SNPs on the promoter region of IL-18 (rs187238 and rs1946518) and one 3’UTR tag SNP (rs1476217) of FGF2 were significantly associated with susceptibility to TAK, with p and OR (95% CI) of 0.0006 and 1.64 (1.25–2.17), 0.03 and 1.28 (1.02–1.64) & 0.016 and 1.33 (1.05–1.67), respectively; while, the two tag SNPs of ANGPT1 gene (rs6469101 and rs16875900) showed a trend ( p = 0.055 & p = 0.051, respectively after permutation based correction). There is robust linkage disequilibrium between the two tag SNPs of IL-18 gene as validated by 1000 genome data of South Asian population; the eQTL effects of these tag SNPs of IL-18 and FGF2 genes on adjacent genes further suggest that these tag SNPs act as genetic risks for development of TAK in South Asians, with possible functional implications towards future biomarker development. Genotype phenotype study by genetic model-based analysis also revealed associations between genotype subsets and clinical features like fever, visual loss, left subclavian and coronary artery involvement in our TAK patients.

Background: Discoid lupus erythematosus (DLE) is a specific cutaneous manifestation of systemic lupus erythematosus (SLE), which results in scarring alopecia of the scalp. Methods: A prospective cross-sectional observational study on scarring alopecia among SLE patients was done between September 2016 and August 2017. The clinical and trichoscopic patterns of scalp DLE among these patients were studied. The DLE lesions were categorised into active and inactive based on clinical features. Trichoscopy was done and photographs were obtained using a non-polarised videodermoscope. Results: There were 26 patients with scalp DLE, out of which 15 patients (57.69%) had active DLE and 11 (42.30%) had inactive DLE. The trichoscopic findings seen were structureless white areas, loss of follicular units, blue-grey dots and globules, follicular keratotic plugs and telangiectasia. The trichoscopic features seen in active versus inactive DLE were blue-grey dots and globules (93.33% vs 63.63%), structureless white areas (93.33% vs 90.90%), loss of follicular units (86.66% vs 72.72%) and follicular keratotic plugs (80% vs 45.45%), yellow dots with arborising vessels (33.33% vs 72.72%), exaggerated honeycomb pigmentation (46% vs 63.63%) and telangiectasia (66.67% vs 54.54%). Scaling (P = 0.033) and blue-grey dots (P = 0.021) were significantly higher in active and yellow dots with arborising vessels (P = 0.047) in inactive DLE. Conclusions: On comparing trichoscopic features between active and inactive DLE scaling and blue-grey dots were significantly higher in active and yellow dots with arborising vessels in inactive DLE.

Remote monitoring technologies (RMTs) are an emerging tool for assessing, monitoring, and following up on patients with chronic diseases including autoimmune rheumatic diseases (AIRDs). The best use of these exponentially expanding technologies warrants optimum evidence. Rheumatoid arthritis (RA) is a chronic inflammatory process that requires close monitoring of disease activity, response to treatment, and the potential adverse effects. Though there are several studies that have explored RMTs in RA, there is little head-to-head comparison between the individual technologies or the standard of care. Before investing in potentially high-cost strategies like RMTs, it is prudent to estimate their pragmatic role in the management and potentially with long-term follow-up including drug titration. A thorough search of the literature was conducted across PubMed/MEDLINE, Scopus, and WebOfScience databases for recent and relevant literature looking at the acceptance, practical utility, and outcomes in RA using RMTs. This scoping review aims to summarize the current level of evidence in favor of RMTs, estimate real-world benefits and costs, potential hazards and limitations, and finally, identify future studies needed before endeavoring to mainstream RMTs. It emphasizes randomized trials using RMTs, patients reported outcomes and disparities in the usage of RMTs.

Aim: The present study aimed to evaluate the factors influencing the referral delay in patients with primary Sjogren’s syndrome (Sjogren’s) and systemic sclerosis (SSc). Materials and Methods: The independent, multicentre, cross-sectional study collected data from seven centres across India through the Indian Rheumatology Association (IRA) database. The patient-related factors and referral factors were determined based on the patient narrations. Based on the patient’s income, a modified version of the Prasad scale was employed to classify them according to socioeconomic status. Results: The study included 118 patients with Sjogren’s and 166 patients with SSc. Approximately 60% of patients with SSc and Sjogren’s received rheumatology specialty care more than 6 months after symptom onset. The primary reasons for this delay were identified as a lack of awareness of rheumatology specialty care among patients (Sjogren’s: 61%; SSc: 74%) and disease management by other specialists (Sjogren’s: 75%; SSc: 62%) rather than rheumatologists. Additionally, over 25% of primary care practitioners were unaware of rheumatology specialty services, and a similar percentage of patients were not diagnosed with rheumatic diseases by their primary care physicians. Patients with delayed referrals for Sjogren’s exhibited higher rates of haematologic, oral, and non-articular pain. Similarly, in SSc patients, delayed referral was associated with a significantly higher prevalence of skin involvement ( P < .01). Conclusion: Patient referrals to other specialties and a lack of knowledge about rheumatology were the primary causes of referral delays. Educating primary care physicians and facilitating direct referrals to rheumatology specialists could help reduce these delays. The study findings may help in stratifying interventions to improve early referral and access to rheumatology specialty care for patients with Sjogren’s and SSc.

The relapses and refractory disease are a challenge in the management of patients with Takayasu arteritis (TAK). We quantified pathogenic CD4 + memory T helper cells bearing surface markers CD161 and/or p-glycoprotein (MDR1) in patients with TAK. Peripheral blood mononuclear cells of 21 patients with TAK and 16 age-matched controls were stained with anti-CD3, anti-CD4, anti-CD45RA, anti-CD161 and anti-p-glycoprotein antibodies and subjected to flow cytometry by FACS ARIAIII. Eighteen patients underwent follow-up immunophenotyping. Intracellular staining for interleukin-17 and interferon-γ was performed for 18 patients and 11 controls. Surgical arterial biopsies of 6 TAK and 5 non-inflammatory controls were subjected to immunohistochemistry with anti-CD161 and anti-p-glycoprotein. At baseline the frequency of MDR1 + CD4 + and CD161 + MDR1 + CD4 + memory T cells was higher in TAK than controls ( p = 0.002 and 0.01, respectively). After stimulation, the frequency of IFN-y + CD161 + cells was higher in TAK than controls ( p = 0.028). Modal fluorescence intensity of CD161 + MDR1 + CD45RA − CD4 + cells was higher in active as compared with stable disease ( p = 0.041). At 6 months, MDR1 + and CD161 + MDR1 + memory CD4 + T cells decreased significantly only in patients who had complete/partial response to treatment ( p = 0.047 and 0.02, respectively). To conclude, MDR1 + and MDR1 + CD161 + CD4 + memory T-helper cells are increased in patients with TAK. These cells decreased only in patients with response to treatment during subsequent follow-up.

BACKGROUND:The status of vascular lesion treatment using percutaneous intervention (PI) in Takayasu arteritis (TAK) remains unresolved. OBJECTIVES:This study sought to develop PI strategies appropriate for TAK. METHODS:A prospectively maintained single-center database of TAK PI procedures from 1996 to 2022 was analyzed retrospectively. Obstructive lesions were treated by elective stenting (using bare or covered stents), balloon angioplasty (BA), or cutting-balloon angioplasty (CBA), with adjunctive stenting for suboptimal BA or CBA results. PIs were repeated in restenotic lesions until sustained success was obtained. Aortic or peripheral aneurysms and spontaneous aortic dissections were treated with covered stents or endografts. Immunosuppressive therapy, started before PI, was continued long term. RESULTS:A total of 942 patients underwent PI to treat 2,450 arterial lesions (2,365 stenoses or occlusions, 85 aneurysms or dissections) in 630 subclavian or axillary, 586 renal, 463 aortic, 333 carotid, 188 mesenteric, 116 iliac, 71 coronary, and 63 other arteries; 3,805 PIs were performed (1.55 PIs per lesion; range 1-7 PIs per lesion). Early success was obtained in 2,262 (92.3%), and late success in 1,460 (84.5%) of 1,727 lesions with a median of 39 months (IQR: 15-85 months) of follow-up. Repeated PIs increased late success in obstructive lesions from 48.6% to 83.3%. A total of 1,687 elective stenting lesions achieved 88% late success with 1.49 PIs per lesion; covered stents (1.18 PIs per lesion) restenosed less than bare stents (1.51 PIs per lesion; P < 0.001). A total of 183 (36%) of 513 BA-treated lesions had good outcomes without adjunctive stenting; 122 CBA-treated lesions had 19% dissections and 8% ruptures or pseudoaneurysm formations. Aneurysms or dissections had 91.3% late success after PI. A total of 472 complications occurred in 415 (17%) lesions; 375 (79%) were resolved. CONCLUSIONS:Most vascular lesions in TAK can be effectively, safely, and durably treated using predominantly stent-based PI strategies.

Objective To compare the clinical and angiographic responses of mycophenolate mofetil (MMF) versus methotrexate (MTX) in Takayasu arteritis (TAK). Methods This was an open-label, outcome assessor-blinded trial. Adult patients with active TAK were randomized 1:1 to MMF 1 g twice daily or MTX 20 mg once weekly by a computer-generated program. All patients were started on 0.5 mg/kg of steroids with a predetermined tapering protocol. The primary outcome was the treatment response as defined by Indian Takayasu arteritis score at 9 months. The secondary end points included the time to first failure and angiographic progression. Results A total of 52 patients (26 in each arm) were recruited. The rate of responders was 71.43% (15/21) in the MMF arm and 63.64% (14/22) in the MTX arm (P = .58). The median time to the first failure was 9 months (range: 3-9) and 4.5 months (range: 3-9) in the MMF and MTX arms, respectively (P = .052). In both groups, 15% of patients (n = 3) had a progressive disease in angiography. Conclusions The results showed numerically better outcomes favouring MMF, with a longer time to the first failure than MTX (9 months versus 4.5 months, P = .052). No significant difference was seen in the angiographic outcomes.

Fibrosis is a result of chronically activated fibroblasts leading to the overproduction of extracellular matrix (ECM), causing tissue hardening and loss of organ function. Systemic sclerosis (SSc) is a fibrotic skin disease marked by inflammation, autoimmunity and vasculopathy along with progressive fibrosis of the skin and internal organs. A major bottleneck in understanding the etiology of SSc has been the lack of a holistic animal model that can mimic the human SSc disease. We found that the transcription factor Snail is overexpressed in the epidermis of SSc patients and a transgenic mouse recapitulating this expression pattern is sufficient to induce hallmark clinical features of the human disease. Using this mouse model as a discovery platform, we have uncovered a critical role for the matricellular protein Mindin in fibrogenesis. Mindin is produced by Snail transgenic skin keratinocytes and aids fibrogenesis by inducing inflammatory cytokine and collagen production in resident dermal fibroblasts. Given the dispensability of Mindin in normal tissue physiology, targeting this protein holds promise as an effective therapy for fibrosis.

Abstract The clinical presentation of patients with Takayasu arteritis (TAK), a large vessel vasculitis, is heterogenous and absence on an ideal biomarker renders assessment of disease activity difficult. In the present study we determined the biomarker profile of patients with TAK and subclassified them based on the same. Methods: Serum of consecutive patients with TAK and 36 controls were subjected to bead-based-multiplex assay or ELISA to quantify cytokines or chemokines or growth factors representing various pathophysiological pathways in TAK. The concentration of analytes between patients and controls and among various subsets of patients were compared. Unbiased clustering of patients was performed by dimensionality reduction methods and correlation networks were constructed. The surgical arterial biopsies of a subset of patients were examined for the extent of inflammation, fibrosis and myxomatous changes in arterial wall and the changes were correlated with cytokine concentration. Results: 85 patients with TAK [66 females, mean age: 28.8 ± 8.9 years, symptom duration of 24 months (IQR: 8–48 months)] and 36 controls were recruited. Levels of B cell antigen (BCA-1) and Pentraxin-3 were higher in patients than controls after applying correction for multiple testing (p < 0.02 for both). IL18 levels were highest in type 5 subtype (p = 0.015) while angiopoietin-2 and BCA-1 levels were highest in type 4 disease (p = 0.015, 0.003 and 0.009 respectively). The level of angiopoietin-2 was higher in patients with active disease (n = 52) than stable disease at baseline (p = 0.007) while IL6 and MMP-2 were paradoxically lower in patients with active disease (p = 0.029 and 0.021 respectively). Serum IL18 and IL2Rα levels trended to correlate positively with intensity of inflammation in the studied samples of aortic tissues. Among treatment naïve patients, those with lower concentration serum IL15, IFNγ and IL12p70 separated into one cluster. The angiogenic factors, MMP-9 and pentraxin-3 demonstrated interconnectedness in patients with active disease and not in those with stable disease. Conclusions: Patients with TAK have varied biomarker profile that depends on angiographic type and intensity of inflammation. While BCA-1 and Pentraxin levels were higher in TAK as compared with controls, angiopoietin-2, Il-6 and MMP-2 levels differentiated active from stable TAK. The biomarkers interconnected among each other differently in active and stable patients.