- Indian Rheumatology association
Mahabaleshwar Mamadapur MD, DM (Clinical Immunology and Rheumatology)
Assistant Professor, Dept of Clinical Immunology and Rheumatology, JSS Medical College and Hospital, JSSAHER, Mysore
Study in focus 1: A Multiomic Analysis to Identify Drivers of Subclinical Vascular Disease in Systemic Lupus Erythematosus (1)
Systemic lupus erythematosus is associated with a significantly increased risk of cardiovascular disease, largely as a result of immune dysregulation. The traditional risk factors alone do not explain this increased risk. This study examined the molecular drivers of subclinical vascular disease in SLE, with a focus on gene expression and serum protein biomarkers.
This comprised 77 patients with SLE and 27 healthy controls. Comprehensive vascular assessment included the following: Cardio-ankle vascular index [CAVI] (indices of arterial stiffness), Target-to-background ratio [TBR] (using PET/CT to quantify inflammation), and coronary plaque burden assessed by Coronary computer tomography angiography [CCTA]. Blood samples were analyzed for relevant genes by RNA sequencing and relevant proteins through proteomics.
Key Findings:
Conclusion: This study identified immune and metabolic pathways contributing to subclinical vascular disease in SLE. The findings highlight potential biomarkers for early detection and new therapeutic targets to mitigate CVD risk in SLE patients.
Study in focus 2: A Genome-Wide Association Study Suggests New Susceptibility Loci for Primary Antiphospholipid Syndrome (2)
Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder caused by the presence of antiphospholipid antibodies, recurrent thrombotic events, and complications during pregnancy. Even though the genetic factors contribute to the disease, genome-wide studies are not available. The
purpose of this study was to identify novel genetic loci for PAPS and to improve our understanding of its mechanisms. A total of 482 patients with PAPS and 5,003 European-ancestry controls from five cohorts were used. Genomic DNA was obtained from blood samples through DNA extraction, and subsequent analysis was conducted by applying genome-wide association studies. Data integrity was ensured using stringent quality control procedures. State-of-the-art statistical analyses-including meta-analysis and conditional regressions-were applied to highlight the significant associations. Functional annotation and enrichment analysis further validated these genetic variants regarding their biological implications.
Key Findings
1. Genetic Associations
Two major loci were identified: one in HLA class II region, close to the gene for HLA-DRA, and another within the STAT1-STAT4 genes. The HLA-DRA variant was associated with enhanced expression of several HLA class II genes in immune, vascular, and nervous tissues. Thirty-four additional loci were suggestively linked to PAPS, including genes associated with immune responses and vascular functions.
2. Functional Insights
The identified genetic loci demonstrated significant enrichment in immune-related pathways, indicating their possible role in disease development. Epigenetic markers and changes in gene expression linked to disease-associated variants were highlighted, providing insights into potential biological mechanisms.
3. Comparison with Other Diseases
PAPS exhibited genetic similarities with other autoimmune disorders, including neuromyelitis optica, systemic sclerosis, and Sjögren’s syndrome.
4. Population Risk
There was significant variation in each of the different populations when subjected to cumulative genetic risk score analysis. Surprisingly, individuals from East Asian and African descent groups had a higher genetic risk for PAPS compared to the European and South Asian groups. This may be indicate population-specific genetic factors behind the occurrences of diseases with varying manifestations.
Conclusion:
This study stands as the most extensive genome-wide analysis of PAPS conducted to date, uncovering critical genetic loci and pathways. The findings provide valuable insights into the genetic foundations of PAPS and its connections to other autoimmune diseases, offering a foundation for future research and potential therapeutic advancements.
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