Increased serum IL-2, IL-4, IL-5 and IL-12p70 levels in AChR subtype generalized myasthenia gravis

Abstract

Background Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions. Cytokines play important roles in facilitating the immune response and augmenting the pathogenic antibody production. The current study aims to sensitively characterize the serum levels of cytokines with very low concentration in generalized MG (gMG). Methods Using ultrasensitive single-molecule arrays (SIMOA), we measured serum IL-2, IL-4, IL-5 and IL-12p70 in 228 participants including 152 immunotherapy-naïve anti-acetylcholine receptor (AChR) subtype gMG from Huashan MG registry and 76 age-matched healthy controls. Subgroup analysis was then performed by stratifying patients according to the onset ages, MGFA classification, disease duration at baseline. Results Serum IL-2, IL-4, IL-5 and IL-12p70 levels were significantly elevated in gMG compared to controls (0.179 pg/mL versus 0.011 pg/mL, P < 0.0001; 0.029 pg/mL versus 0.018 pg/mL, P = 0.0259; 0.215 pg/mL versus 0.143 pg/mL, P = 0.0007; 0.132 pg/mL versus 0.118 pg/mL, P = 0.0401). Subgroup analysis revealed that IL-2 levels were slightly elevated in gMG with MGFA II compared to MGFA III/IV (0.195 pg/mL versus 0.160 pg/mL, P = 0.022), as well as elevated levels of IL-2 (0.220 pg/mL versus 0.159 pg/mL, P = 0.0002) and IL-5 (0.251 pg/mL versus 0.181 pg/mL, P = 0.004) in late-onset gMG compared with the early-onset gMG. gMG patients with a long duration had a significant increased serum IL-12p70 than those with a short duration (0.163 pg/mL versus 0.120 pg/mL, P = 0.011). Conclusion Serum IL-2, IL-4, IL-5 and IL-12p70 levels were increased in AChR subtype gMG using ultrasensitive measurement. Serum cytokines with very low concentrations may provide as potential biomarkers in stratifying gMG patients in future prospective cohort studies.

NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing

“…Some studies found a less pronounced interferon alpha response in patients with severe disease than in those with mild disease 36,37 , another study reported persistently higher interferon alpha and lambda levels in patients with severe disease than in those with moderate disease 38 , and yet another study found no association between interferon alpha levels and disease severity 39 . These findings highlight the critical importance of highly sensitive and robust assays in exploring the low-abundance portion of the proteome that is enriched for important cytokines, such as interferons 40 .…”

NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing

“…Some studies found a less pronounced interferon alpha response in patients with severe disease than in those with mild disease 41,42 , another study reported persistently higher interferon alpha and lambda levels in patients with severe disease than in those with moderate disease 43 , and yet another study found no association between interferon alpha levels and disease severity 28 . These findings highlight the critical importance of highly sensitive and robust assays in exploring the low-abundance portion of the proteome that is enriched in important cytokines, such as interferons and IL4 44 .…”

Recombinant Acetylcholine Receptor Immunization Induces a Robust Model of Experimental Autoimmune Myasthenia Gravis in Mice

“…In respect to the T cell compartment, in previous studies of EAMG, increased numbers of IL17 producing CD4 T cells were detected in the blood of EAMG mice [ 28 ]. In humans, CD4 T cells display increased production of IL4, IL17 and IL21 [ 29 , 30 ] and increased serum levels of these cytokines were detected [ 31 ]. In the context of EAMG, this dysregulated T cell response could create an inflammatory milieu conducive to the generation of antibody-producing B cells.…”