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Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations.

ABSTRACT: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to characterize MPs more completely, we investigated 280 SLE patients and 280 individually matched controls. MPs were measured with flow cytometry and phenotyped according to phosphatidylserine expression (PS⁺/PS^-), cellular origin and inflammatory markers. MPs, regardless of phenotype, are 2-10 times more abundant in SLE blood compared to controls. PS^- MPs predominated in SLE, but not in controls (66% vs. 42%). Selectively in SLE, PS^- MPs were more numerous in females and smokers. MP numbers decreased with declining renal function, but no clear association with disease activity was observed. The striking abundance of MPs, especially PS^- MPs, suggests a generalized disturbance in SLE. MPs may be regarded as "liquid biopsies" to assess the production and clearance of dead, dying and activated cells, i.e. pivotal events for SLE pathogenesis.

SUBMITTER: Mobarrez F

PROVIDER: S-EPMC5078765 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations.

Mobarrez Fariborz F Vikerfors Anna A Gustafsson Johanna T JT Gunnarsson Iva I Zickert Agneta A Larsson Anders A Pisetsky David S DS Wallén Håkan H Svenungsson Elisabet E

Scientific reports 20161025

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to c ...[more]

PMID: 27777414

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Project description:Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7 × 10(-9), OR = 1.40 (95% CI = 1.25-1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67-0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7 × 10(-5), OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs1217414 and rs3765598 may be associated with SLE. Further studies are required to confirm the involvement of rs2476601 with aCL IgG.

Dataset Information

Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations.

Publications

Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations.

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