Background SLE is a multisystem heterogeneous autoimmune disease characterised by production of antibodies to cellular components, innate and adaptive immune alterations and dysregulation of cytokine production. Multiplex immunoassay is a… Click to show full abstract
Background SLE is a multisystem heterogeneous autoimmune disease characterised by production of antibodies to cellular components, innate and adaptive immune alterations and dysregulation of cytokine production. Multiplex immunoassay is a useful tool for the detection of ANA associated with different clinical phenotypes and cytokine profiles in SLE. Objectives To evaluate the relationship between ANA subpopulations, clinical subtypes and cytokine profiles in SLE. Methods We studied 61 patients with SLE (2012 SLICC classification criteria) (8M/53 F), median and interquartile range (25th—75th percentile) of age 30.0 (27.0–45.0) years, disease duration 90.5 (12.5–168.0) months, SLEDAI 2K score 8.0 [4.0–16.0]; SLICC damage index score 1.0 (0–2.0) and 28 healthy donors. Serum samples were analysed for SLE-associated ANA (anti-dsDNA, anti-Sm, anti-chromatin, anti-SS-A/Ro 52 kDa and 60 kDa, anti-SS-B/La, anti-RNP-70, anti-ribosomal P – anti-RibP) using multiplex bead-based immunoassay system BioPlex 2200 (ANA Screen; Bio-Rad Laboratories Inc., USA). The levels of cytokines were determined with Bio-Plex 200 technology (Human Grp I Cytokine 27-plex panel; Bio-Rad Laboratories Inc., USA). Results Serum levels of anti-dsDNA, anti-chromatin, anti-Sm and anti-RibP antibodies were positively correlated with SLEDAI-2K scores (r=0.6, r=0.7, r=0.4, r=0.3, p<0.05). Antibodies to dsDNA, chromatin, Sm and SS-A/Ro was most often detected in patients with dermatologic (59%, 57%, 32%, 43%), renal (64%, 66%, 36%, 38%) and neuropsychiatric (61%, 61%, 28%, 39%) manifestations of SLE. Increased serum concentrations of IFN-inducible chemokines: IP 10 and MCP1 were associated with high anti-dsDNA (r=0.3), anti-chromatin (r=0.5), anti-Sm (r=0.5), anti-SS-B/La (r=0.3), anti-RibP (r=0.4) (p<0.05) and anti-Sm (r=0.3), anti-SS-B/La (r=0.3), anti-RibP (r=0.3) (p<0.05) antibodies levels. Hyperproduction of chemokines RANTES and IL-8/MIP-1α negatively correlated with anti-dsDNA (r=−0.3), anti-chromatin (r=−0.3) (p<0.05) and anti-SS-A/Ro (r=−0.3) (p<0.05) antibodies levels, respectively. Low levels of pro-inflammatory cytokines IL-1β, IL-15 were negatively associated with the presence of antibodies to dsDNA and RibP (r=−0.3) (p<0.05), but a positive correlation was found between the levels of anti-inflammatory cytokines IL-10, IL-1ra and anti-Sm (r=0.3), anti-SS-B/La (r=0.3), anti-SS-A/Ro (r=0.3) (p<0.05) antibodies titers. Elevated concentration of GM-CSF was negatively correlated with serum level of antibodies to Sm (r=−0.3) (p<0.05). Conclusions These data suggest that the presence of ANA clusters may identify patients with distinct clinical subtypes and cytokine profiles and can reflecting different pathways of immune dysregulation in SLE. Disclosure of Interest None declared
               
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