Table 2.

Genetic alterations and their possible clinical implications in patients with ANCA-associated vasculitisa

ReferenceGene Encoding forGenetic AlterationDiagnosisClinical Implication of Alteration
Hagen et al. (175)HLAHLA-DR13DR6 antigen decreaseWG and MPAUnknown
Spencer et al. (183)HLA-DR3 decreaseWG and MPAInhibits autoreactive T cell elimination and inhibition of induction of antigen-specific T suppressor cells
Spencer et al. (183)HLA-DQw7 increaseWG and MPAInfluences duration of immune response
Gencik et al. (176)HLA-DRB1*04 increaseWG with ESRDContributes to severe courses of WG
Boki et al. (156)HLA-DR1 antigen increaseWGUnknown
Papiha et al. (177)HLA-DR1-DQw1 increaseWGUnknown
Katz et al. (178)HLA-B8 increaseWGPredisposes to abnormal hypersensitivity reaction
Cotch et al. (179)HLA-B50 increaseWGUnknown
Cotch et al. (179)HLA-DR9 increaseWGIncreases susceptibility to allergy
Elkon et al. (180)HLA-DR2 increaseWGPredisposes to abnormal hypersensitivity reaction
Spencer et al. (183)HLA-DR4DQ7 increaseWG and MPAResults in transient positive ANCA and high TNF-α synthesis
Jagiello et al. (181)HLA-DPB1*0401 increaseWGStimulates development of granulomatous inflammation
Jagiello et al. (181)HLA-DPB1*0301 decreaseWGStimulates development of granulomatous inflammation
Tsuchiya et al. (182)HLA-DPB1*0901 increaseMPAUnknown
Gencik et al. (176)HLA-DRB1*13 decreaseWG and MPAMay modulate the response of autoreactive T cells
Gencik et al. (176)HLA-DQB1*0603 decreaseWG and MPA
Jagiello et al. (181)ApoptosisCasp14WGShifts the balance of apoptosis, resulting in loss of self-tolerance or persistent inflammation
Jagiello et al. (181)Ripk1WGShifts the balance of apoptosis, resulting in loss of self-tolerance or persistent inflammation
Dijstelbloem et al. (184)Fcγ receptorPolymorphism of FcγRIIa: Homozygosity for R131 formWGDecreases FcR-mediated clearance, promoting chronic nasal carriage of S. aureus and stronger interaction with ANCA, increasing relapse risk
Dijstelbloem et al. (184)Polymorphism of FcγRIIIa: Homozygosity for R158 formWGDecreases FcR-mediated clearance, promoting chronic nasal carriage of S. aureus and stronger interaction with ANCA, increasing relapse risk
Persson et al. (185)ComplementC3F increaseWG and MPAInfluences antibody production
Persson et al. (185)C4A3 increaseWG and MPAModulates immune response
Papiha et al. (177)C4B increaseWGModulates immune response
Gencik et al. (186)Adhesion of PMNPolymorphism of CD18, AvaII + allele overexpressionMPO-ANCAIncreases adhesion, facilitating degranulation and respiratory burst
Huang et al. (188)T cell geneMicrosatellite of CTLA-4: Shortest allele decreaseWGIncreases T cell activation
Zhou et al. (191)Microsatellite of CTLA-4: Shortest allele decreaseWGIncreases T cell activation and clonal expansion
Giscombe et al. (192)CTLA-4 SNP in the promoter regionPR3-ANCAResults in persistence of T cell activation
Spriewald et al. (194)Polymorphism of CTLA-4WG with ESRDIncreases T cell activation
Bartfai et al. (193)Cytokine genesPolymorphism in IL-10 increaseWG and MPAThis Th2-type cytokine is important in B cell proliferation and differentiation but can also exert anti-inflammatory activity
Murakozy et al. (195)Polymorphism in IL-10 increaseWGDecreases IL-10 level with loss of inhibition of Th1 responses and monocyte function
Borgmann et al. (197)IL-1β increase and IL-1R antagonist decreasePR3-ANCA with ESRDProinflammatory genotype causes proinflammatory responses
Spriewald et al. (194)IFN-γ polymorphism increaseWGIncreases IFN-γ production and modulates proinflammatory responses
Spriewald et al. (194)IFN-γ polymorphism increaseWG with ESRDModulates disease susceptibility
Spriewald et al. (194)TNF-α polymorphism increaseWGIncreases TNF-α production and modulates proinflammatory responses
Murakozy et al. (195)TGF-β1 increaseWGProinflammatory genotype causes proinflammatory responses
Csernok et al. (196)TGF-β1 increaseWG and MPAInducing angiogenesis and being strongly chemotactic, TGF-β1 serves as a proinflammatory factor
Esnault et al. (174)PR3 inhibitorHomozygous and heterozygous α1-AT deficiencyPR3-ANCAContributes to disease induction
Gencik et al. (199)PR3Overexpression of the promoter regionWGProbably increases PR3 protein expression
Reynolds et al. (200)MPOPolymorphism in the promoter regionMPO-ANCAProbably increases MPO protein expression
  • a ANCA, antineutrophil cytoplasmic autoantibody; PMN, polymorphonuclear cells; SNP, single-nucleotide polymorphism.