Biomedical subjects

Sarfaraz Hasni

Publications and source records attributed to Sarfaraz Hasni.

3 recordsLinked to original sources

PubMed2026

Immunoproteomic Profiling of Autoantibodies and Antibodies against Infectious Agents in Autoimmune Diseases.

Prior research investigated limited antibody sets within individual autoimmune diseases. Using the Nucleic-Acid Programmable Protein Array platform, we measured antibodies against 280 human, 40 viral, and 15 bacterial antigens in serum from 237 patients with 8 autoimmune diseases, including autoimmune gastritis (AG), autoimmune thyroiditis (AT), celiac disease (CD), idiopathic inflammatory myopathies (IIM), type 1 diabetes mellitus (T1D), rheumatoid arthritis (RA), Sjögren's disease (SjD), and systemic lupus erythematosus (SLE), and 112 controls. Candidate antibodies were identified by combining Firth logistic regression and machine learning. We identified disease-specific antibodies, ranging from 3 in IIM to 13 in SLE for IgG and 1 in CD to 13 in AG for IgA. Additionally, 63 IgG and 44 IgA antibodies were shared across two or more diseases. Notably, two IgG autoantibodies overlapped in up to five diseases: directed against STNM4 (SLE, SjD, T1D, CD, and RA) and TRIM21 (SLE, SjD, IIM, CD, and RA); and three IgA antibodies in up to seven diseases: directed against H1N1 Influenza A virus NP (IIM, SjD, AG, T1D, CD, RA, and AT) and Coxsackievirus B3MK012537 and Enterovirus C PVgp1 (IIM, SjD, AG, T1D, CD, SLE, and RA). These findings underscore the potential of antibody profiling in autoimmune disease characterization and biomarker discovery.

Humans↗

PubMed2026

Dysregulation of U12-Type Splicing in Lupus Neutrophils.

OBJECTIVE: Neutrophil dysfunction is a hallmark of systemic lupus erythematosus (SLE), but its molecular basis remains unclear. This study explores transcriptional and posttranscriptional changes in low-density granulocytes (LDGs), a proinflammatory neutrophil subset expanded in SLE, focusing on NADPH oxidase (Nox) function and minor intron splicing. METHODS: LDGs and normal-density granulocytes (NDGs) were isolated from patients with SLE and healthy controls (HCs). CYBA (p22phox) expression was evaluated at transcript and protein levels. Nox activity was measured using luminol assays. Bulk RNA sequencing (RNA-seq) and rMATS software were used to assess alternative splicing, particularly of U12-type intron-containing genes. RESULTS: CYBA expression was reduced in SLE LDGs (n = 11) compared to SLE and HC NDGs (n = 6), with levels resembling those in chronic granulomatous disease neutrophils. SLE LDGs exhibited impaired Nox activity (n = 7 SLE, n = 12 HC). CYBA is a U12 intron-containing gene, and transcriptomic analysis revealed broad down-regulation of this gene class in SLE LDGs, suggesting minor spliceosome dysfunction. rMATS analysis showed increased U12-type intron retention and widespread splicing defects-including exon skipping and mutually exclusive exon use-in genes such as GBP5, MAEA, and STX10. These abnormalities were validated in an independent long-read RNA-seq data set from SLE peripheral blood mononuclear cells. Importantly, splicing disruptions correlated with disease activity and autoantibody profiles. CONCLUSION: Impaired U12-dependent splicing may contribute to neutrophil dysfunction in SLE, potentially via defective oxidative burst and altered immune regulation. These findings highlight the minor spliceosome as a novel player in lupus pathogenesis.

Humans↗

PubMed2025

Next generation sequencing analysis reveals complex genetic architecture of childhood-onset systemic lupus erythematosus.

OBJECTIVES: Our current understanding of the genetic architecture of childhood-onset SLE (cSLE) is limited by a dearth of comprehensive genomic studies in cSLE. We have quantified the number of known rare and common SLE risk variants in a diverse cSLE cohort. We characterised type I interferon (IFN) gene expression scores along with genomic data. METHODS: We performed whole genome sequencing on 83 patients with cSLE and 109 unaffected parents and analysed sequences for known common and rare SLE-associated risk variants. Type I IFN gene expression was quantified on a subset of patients. We investigated the relationship between clinical phenotype, genomic profile and type I IFN signatures in this cohort. RESULTS: Patients with cSLE were enriched for common SLE risk variants compared with unaffected parents and controls. We identified rare SLE risk variants in 11% of individuals with cSLE; those with rare variants had earlier disease onset (<12 years) than those without variants. Patients with cSLE had elevated type I IFN gene expression compared with unaffected parents and controls, even though most patients were treated with immunosuppressive therapy. CONCLUSIONS: Patients with cSLE from this ancestrally and geographically diverse cohort are enriched for common cSLE risk variants compared with controls, and 11% carry a rare variant in known monogenic SLE risk genes. The relationship between rare and common risk variant burden is more complex than previously hypothesised. Our findings indicate that studying patients with cSLE is important for understanding genetic contributions to SLE pathogenesis.

Humans↗