MRI predictors of infectious etiology in patients with unilateral sacroiliitis.

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.

A pilot study of childhood-onset Takayasu arteritis using whole exome sequencing suggests oligogenic inheritance involving classical complement, collagen, and autoinflammatory pathways.

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. Key Points • We identified novel 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 in C3 and COL5A1; this may have implications in disease development, suggesting digenic inheritance. • One patient has homozygous variant in CYBA. • None of the patients were identified to have ADA2 variants.

Coalition for Health and Gender Equity (CHANGE)-a protocol for a global cross-sectional survey of health and gender equity in rheumatology.

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.

Study of pathogenic T-helper cell subsets in Asian Indian patients with Takayasu arteritis.

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.

Angiogenesis related genes in Takayasu Arteritis (TAK): robust association with Tag SNPs of IL-18 and FGF-2 in a South Asian Cohort.

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.

Current Diagnosis and Management of Takayasu Arteritis.

Takayasu arteritis (TA or TAK) is a chronic large vessel vasculitis with predilection to affect the aorta and its branches. The new 2022 ACR/EULAR classification criteria for Takayasu arteritis incorporated imaging characteristics as an absolute requirement. ESR and CRP fails in accuracy as disease activity markers. Pentraxin 3 appears to be a relatively superior biomarker, which correlates with ITAS 2010 as per several studies. PET-CT is also increasingly being studied for assessing disease activity with variable results. The management of TAK involves use of steroids with upfront steroid sparing immunosuppressive agents. MMF is one such conventional DMARD/immunosuppressant with good efficacy and better safety profile, as reported in various cohort studies. Tocilizumab is proved to be a rapid remission inducing agent in refractory Takayasu arteritis in observational studies. TNF inhibitors in many uncontrolled studies showed good responses, and there is a need for good RCTs for confirmation. JAK inhibitors have also been used with success in a few reports.

Mental healthcare for young and adolescent LGBTQ+ individuals in the Indian subcontinent.

The coronavirus disease (COVID-19) pandemic has led to a significant change in the way healthcare is dispensed. During the pandemic, healthcare inequities were experienced by various sections of society, based on gender, ethnicity, and socioeconomic status. The LGBTQ individuals were also affected by this inequity. There is a lack of information on this topic especially in the developing countries. Hence this issue requires further exploration and understanding. Previous literature briefly explored the mental, physical, and emotional turmoil faced by the LGBTQ community on a regular basis. They feared rejection by family and friends, bullying, physical assault, and religious biases. These issues prevented them from publicly speaking about their sexual orientation thereby making it difficult to collect reliable data. Although they require medical and psychological treatment, they are afraid to ask for help and access healthcare and mental health services. Being mindful of these difficulties, this article explores the various underlying causes of the mental health problems faced by LGBTQ individuals, especially, in the Indian subcontinent. The article also examines the status of healthcare services available to Indian sexual minorities and provides recommendations about possible remedial measures to ensure the well-being of LGBTQ individuals.

HPV and molecular mimicry in systemic lupus erythematosus and an impact of compiling B-cell epitopes and MHC-class II binding profiles with in silico evidence.

Epidemiological link between HPV and SLE is evolving. The possibility of HPV infection-induced molecular mimicry and systemic lupus erythematosus (SLE) was elucidated through detailed in silico analyses. Conserved regions in the structural protein sequences of high-risk HPV types were inferred, and sequence homologies between viral and human peptides were identified to delineate proteins implicated in SLE. B-cell epitopes and MHC-class II binding were compiled using Immune Epitope Database and ProPred II analysis tool. Molecular modeling and molecular dynamics/simulation (MDS) were performed using AutoDock Vina and GROMACS, respectively. Sequence alignment revealed 32 conserved regions, and 27/32 viral peptides showed varying similarities to human peptides, rich in B-cell epitopes with superior accessibility, high hydrophilicity, antigenicity and disposition to bind many class-II HLA alleles. Molecular docking of 13 viral peptides homologous (100%) to human peptides implicated in SLE showed that VIR-PEP1 (QLFNKPYWL) and VIR-PEP2 (DTYRFVTS) exhibited higher binding affinities than corresponding human peptides to SLE predisposing HLA-DRB1 allele. MDS of these peptides showed that the viral peptides had superior folding, compactness, and a higher number of hydrogen bonds than human peptides throughout the simulation period. SASA analysis revealed that the VIR-PEP1&2 fluctuated less frequently than corresponding human peptides. MM-PBSA revealed that the VIR-PEP2 complex exhibited higher binding energy than the human peptide complex. This suggests that highly conserved structural peptides of high-risk HPV types homologous to human peptides could compete and bind avidly to the HLA allele associated with SLE and predispose HPV-infected individuals to SLE through molecular mimicry.Communicated by Ramaswamy H. Sarma.

Outcomes of Percutaneous Intervention in Patients With Takayasu Arteritis.

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.

Mindin (SPON2) Is Essential for Cutaneous Fibrogenesis in a Mouse Model of Systemic Sclerosis.

Systemic sclerosis is a fibrotic disease that initiates in the skin and progresses to internal organs, leading to a poor prognosis. Unraveling the etiology of a chronic, multifactorial disease such as systemic sclerosis has been aided by various animal models that recapitulate certain aspects of the human pathology. We found that the transcription factor SNAI1 is overexpressed in the epidermis of patients with systemic sclerosis, and a transgenic mouse recapitulating this expression pattern is sufficient to induce many 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 (SPON2) in fibrogenesis. Mindin is produced by SNAI1 transgenic skin keratinocytes and aids fibrogenesis by inducing early inflammatory cytokine production and collagen secretion in resident dermal fibroblasts. Given the dispensability of Mindin in normal tissue physiology, targeting this protein holds promise as an effective therapy for fibrosis.

Efficacy and safety of colchicine for the treatment of osteoarthritis: a systematic review and meta-analysis of intervention trials.

OBJECTIVE: Colchicine, an approved treatment for gout, has been trialed in many diseases including osteoarthritis (OA) due to its anti-inflammatory effects. However, its efficacy and safety remain unclear in OA. This systematic review and meta-analysis evaluated the efficacy and safety of colchicine for the treatment of OA. METHODS: PubMed, Web of Science, Scopus, and Cochrane Central were searched from inception through September 2022. Two reviewers independently screened for randomized controlled trials (RCTs) comparing colchicine with placebo or other active comparators for the treatment of OA (knee, hand, or hip OA), extracted data, and performed Cochrane risk of bias assessments. RESULT: Nine RCTs for the knee OA and one for the hand OA were identified, consisting of 847 patients (429 in colchicine arms, 409 in control arms). The studies were conducted between 2002 and 2021 with follow-up periods ranging from 2 to 12 months, in India, Iran, Turkey, Australia, Singapore, and Iraq. Moderate-quality evidence showed no clinically important pain reduction with colchicine compared to control (standardized mean difference [SMD], 0.17; 95% confidence interval [CI], - 0.55, 0.22). Moderate-quality evidence showed no improvement in function with colchicine compared to control in knee OA patients (SMD, - 0.37; 95% CI, - 0.87, 0.13). Colchicine showed an acceptable safety profile with AEs/SAEs comparable to control. CONCLUSION: Current evidence does not suggest a benefit of colchicine in reducing pain and improving physical function in the overall cohort of hand/knee OA patients. Future trials should focus on the subgroups of OA patients with local or systemic inflammation and/or mineralization who might benefit from colchicine.

Clinical and angiographic outcomes of Mycophenolate versus Methotrexate in South Asian patients of Takayasu arteritis: Results from an open-label, randomised controlled trial.

OBJECTIVE: To compare the clinical and angiographic responses of Mycophenolate Mofetil (MMF) versus Methotrexate (MTX) in Takayasu arteritis (TAK). METHODS: This was a open label, outcome assessor blinded trial. Adult patients of TAK with active disease were randomized 1:1 to MMF 1g twice daily or MTX 20 mg once weekly, by computer generated program. All patients were started on 0.5 mg/kg of steroids with a predetermined tapering protocol. Primary outcome was treatment response as defined by Indian Takayasu arteritis score at 9 months. Secondary end points included 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=0.58). The median time to 1st failure was 9 months (Range: 3-9) and 4.5 months (range: 3-9) in the MMF and MTX arm respectively (p=0.052). In both groups, 15 % of patients (n=3) had progressive disease in angiography. CONCLUSION: The results showed numerically better outcomes towards MMF, with a longer time to first failure than Methotrexate(9 months versus 4.5 months, p=0.052). No significant difference was seen in the angiographic outcomes.

2022 American College of Rheumatology/EULAR Classification Criteria for Takayasu Arteritis.

OBJECTIVE: To develop and validate new classification criteria for Takayasu arteritis (TAK). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate criteria items, 2) collection of candidate items present at diagnosis, 3) expert panel review of cases, 4) data-driven reduction of candidate items, 5) derivation of a points-based classification score in a development data set, and 6) validation in an independent data set. RESULTS: The development data set consisted of 316 cases of TAK and 323 comparators. The validation data set consisted of an additional 146 cases of TAK and 127 comparators. Age ≤60 years at diagnosis and imaging evidence of large-vessel vasculitis were absolute requirements to classify a patient as having TAK. The final criteria items and weights were as follows: female sex (+1), angina (+2), limb claudication (+2), arterial bruit (+2), reduced upper extremity pulse (+2), reduced pulse or tenderness of a carotid artery (+2), blood pressure difference between arms of ≥20 mm Hg (+1), number of affected arterial territories (+1 to +3), paired artery involvement (+1), and abdominal aorta plus renal or mesenteric involvement (+3). A patient could be classified as having TAK with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the model area under the curve was 0.97 (95% confidence interval [95% CI] 0.94-0.99) with a sensitivity of 93.8% (95% CI 88.6-97.1%) and specificity of 99.2% (95% CI 96.7-100.0%). CONCLUSION: The 2022 American College of Rheumatology/EULAR classification criteria for TAK are now validated for use in research.

2022 American College of Rheumatology/EULAR classification criteria for Takayasu arteritis.

OBJECTIVE: To develop and validate new classification criteria for Takayasu arteritis (TAK). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate criteria items, (2) collection of candidate items present at diagnosis, (3) expert panel review of cases, (4) data-driven reduction of candidate items, (5) derivation of a points-based classification score in a development data set and (6) validation in an independent data set. RESULTS: The development data set consisted of 316 cases of TAK and 323 comparators. The validation data set consisted of an additional 146 cases of TAK and 127 comparators. Age ≤60 years at diagnosis and imaging evidence of large-vessel vasculitis were absolute requirements to classify a patient as having TAK. The final criteria items and weights were as follows: female sex (+1), angina (+2), limb claudication (+2), arterial bruit (+2), reduced upper extremity pulse (+2), reduced pulse or tenderness of a carotid artery (+2), blood pressure difference between arms of ≥20 mm Hg (+1), number of affected arterial territories (+1 to +3), paired artery involvement (+1) and abdominal aorta plus renal or mesenteric involvement (+3). A patient could be classified as having TAK with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the model area under the curve was 0.97 (95% CI 0.94 to 0.99) with a sensitivity of 93.8% (95% CI 88.6% to 97.1%) and specificity of 99.2% (95% CI 96.7% to 100.0%). CONCLUSION: The 2022 American College of Rheumatology/EULAR classification criteria for TAK are now validated for use in research.

Gender equity in rheumatology leadership in the Asia-Pacific.

Objectives: This study aimed to explore gender equity in rheumatology leadership in the Asia-Pacific region as represented by the member national organizations (MNOs) of the Asia-Pacific League of Associations for Rheumatology (APLAR). Methods: We conducted a retrospective cross-sectional review of gender representation among the presidents of MNOs of APLAR in April 2022. We used the official website of each organization to acquire names and terms in the office of current and past presidents of each organization. The binary gender of each president was estimated using the name-to-gender inference platform Gender API (https://gender-api.com/). Proportions of male and female presidents were estimated for each organization. Data were compared for presidencies commencing before and in/after the year 2000. Results: We found a significant gap in gender parity, with most presidents in the region being men (210 of 252, 83%). More than one-third (7 of 19, 36.8%) of the MNOs had all male presidents, although the proportion of women improved from 7 to 25% in/after 2000 (P = 0.0002). A statistically significant increase in female representation was observed in Australia (P = 0.0268, from 7 to 39%) and New Zealand (P = 0.0011, where the proportion of female presidents increased from 0 to 45%), but not in other countries. Conclusion: A significant gap in gender parity exists in rheumatology leadership in the MNOs of APLAR. Trends suggest improvement over the last two decades, although statistically significant improvement is limited to a small number of countries.

Advances in Takayasu arteritis: An Asia Pacific perspective.

Takayasu Arteritis (TA) is a rare form of chronic granulomatous large vessel vasculitis that is more common in Asia compared to other parts of the world. There have been several developments in the field of Takayasu arteritis in relation to genetics, classification, clinical features, imaging, disease activity assessment and management and much of these works have been done in the Asia Pacific region. We will be discussing selected few in the current review.

Genome-Wide DNA Methylation Profiling in CD8 T-Cells and Gamma Delta T-Cells of Asian Indian Patients With Takayasu Arteritis.

Background: Takayasu's Arteritis (TA) is a chronic inflammatory disease that affects aorta and its main branches at their origin. Genetic, pathological and functional studies have shown that CD8 and Gamma delta (γ/δ) T-lymphocytes are involved in inflammatory processes in affected regions of arteries causing vascular damage. The molecular function of these lymphocytes remains unclear and currently no epigenetic studies are available in TA. We primarily performed genome wide methylation analysis in CD8 T cells and γδ T cells of patients with TA and compared with healthy controls. Methods: We recruited 12 subjects in each group namely TA patient and healthy controls. Blood samples were collected after obtaining informed written consent. CD8 T cells and γδ T cells were separated from whole blood. DNA extracted from these cells and were subjected to bisulfite treatment. Finally, bisulfite treated DNA was loaded in Infinium Methylation EPIC array. Bioinformatics analysis was used to identify differential methylation regions which were then mapped to genes. Results: Interleukin (IL)-32 and Lymphotoxin-A were genes significantly hypomethylated in CD8 T-cells. Anti-inflammatory cytokine genes, IL-10, IL-1RN and IL-27 were hypomethylated in γδ T cells of TA patients as compared to healthy controls. Gene enrichment analysis using Gene Ontology (GO) database and Kyoto Encyclopaedia of Genes and Genomes (KEGG) identified that genes involved in T-cell receptor signalling pathways were hypomethylated in CD8 T-cells and hypermethylated in γδ T cells of TA patients. Conclusion: CD8 T-cells might play a major role in immunopathogenesis of inflammation in TA, whereas γδ T cells may play a regulatory role.

Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies.

OBJECTIVE: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. METHODS: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. RESULTS: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). CONCLUSION: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.