Association of MICA-129Met/Val polymorphism with clinical outcome of anti-TNF therapy and MICA serum levels in patients with rheumatoid arthritis

Abstract

MHC class I polypeptide-related sequence A (MICA) is a stress-induced protein involved in activation of NK and T cells through interaction with NKG2D receptor. These molecules are atypically expressed in synovium of patients diagnosed with rheumatoid arthritis (RA). A total of 279 patients with RA, qualified to TNF-blockade therapy, were genotyped for MICA rs1051792 SNP. The effectiveness of anti-TNF agents was assessed with European League Against Rheumatism criteria. Significant relationship between MICA rs1051792 and outcome of TNF-blockade therapy has been found. The MICA rs1051792 GG genotype was overrepresented in patients non-responsive to anti-TNF drugs in comparison with other genotypes (p = 0.010). On the other hand, beneficial therapeutic response was more frequently detected among RA subjects possessing heterozygous genotype than those with homozygous genotypes (p = 0.003). Furthermore, increased MICA concentrations in serum were observed in patients possessing MICA rs1051792 GG genotype as compared with those with GA or AA genotypes (p = 1.8 × 10 −5). The results from this study indicate the potential influence of MICA rs1051792 polymorphism on modulation of therapeutic response to TNF-blockade treatment in RA.

Shared epitope and polymorphism of MICA and NKG2D encoding genes in Greek and Polish patients with rheumatoid arthritis

“…On the other hand, these relationships between anti-CCP and RF positivity and MICA GG homozygosity detected in Greeks were not seen in the Polish group of RA patients. Note, however, the results of our previous study by Iwaszko et al documenting that MICA rs1051792 polymorphism can affect the efficiency of anti-tumour necrosis factor (TNF) therapy in Polish patients [21]. Thus this MICA polymorphism seems to play a significant role also in Polish RA patients.…”

“…For the past few years, non-classical HLA polymorphism, including MICA and NKG2D, has been investigated in Polish patients with RA [ 21 , 22 , 31 ]. As those publications were focused only on one population, there is still a lack of knowledge about the effect of these genetic factors in Greeks [ 11 , 26 ].…”

“…Note, however, the results of our previous study by Iwaszko et al . documenting that MICA rs1051792 polymorphism can affect the efficiency of anti-tumour necrosis factor (TNF) therapy in Polish patients [ 21 ]. Thus this MICA polymorphism seems to play a significant role also in Polish RA patients.…”

“…Our recent findings regarding the effect of MICA [ 21 ] and NKG2D polymorphism on RA treatment outcome [ 22 ] have prompted us to analyse and compare the genetic variability of Greek and Polish patients with respect to the presence of the HLA-DRB1 SE as well as MICA and NKG2D variants.…”

Current Understanding of an Emerging Role of HLA-DRB1 Gene in Rheumatoid Arthritis–From Research to Clinical Practice

“…Apart from the above-mentioned HLA-DRB1 variants, the influence of multiple genes' polymorphisms on the effectiveness of applying anti-TNF-α has been described. They were within the following loci: TNF, TNFR1B (tumor necrosis factor receptor 2), interleukin-6 (IL-6), interleukin-10 (IL-10), TRAF1 (TNF Receptor Associated Factor 1), nuclear factor κB (NF-κB), encoding TLR signaling pathways (TLR2, TLR4, TLR5, CHUK, MyD88, IRAK3), Fc receptors for IgG immunoglobulins (FCGR2A, FCGR3A), NLRP3-inflammasome (NLRP3, CARD8), PTPRC (encoding protein tyrosine phosphatase), PDE3A-SLCO1C1 (encoding intracellular cyclic nucleotide signals regulator), CD84 (encoding B cell receptor), DHX32 (encoding putative RNA helicase), RGS12 (encoding regulator of G protein signaling), MICA (MHC class I polypeptide-related sequence A) [150,[167][168][169][170][171][172][173][174]. Despite the fact that all anti TNF-α agents target the same cytokine, there are differences in the effectiveness of particular drugs in the various group of patients.…”