TNFalpha genotype influences development of IgA-ASCA antibodies in Crohn's disease patients with CARD15 wild type.
A typical feature of Crohn's disease (CD) patients is the development of antibodies against self- (PAB) or exogenous (ASCA) antigens, a process in which mucosal cytokine expression pattern might be involved. On the other hand, mutations in CARD15, a genetic risk factor for CD, alter cytokine production in response to bacterial infection. In the present study, we evaluated the role of functionally relevant IL-10 and TNFalpha gene polymorphisms in the synthesis of these antibodies and their relationship with CARD15 mutations. In CARD15 wild type patients, high TNFalpha producer genotypes protect against IgA-ASCA development, whereas an inverse association was observed in autoantibody synthesis (PAB). These associations were not observed in patients with CARD15 mutations, probably due to the lack of TNFalpha release as a consequence of the failure of CARD15 protein to recognize the peptidoglycan. Thus, we proposed a CARD15-TNFalpha circuit that might play a role in mucosal immune surveillance.
Castro-Santos
Patricia
P
Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
Mozo
Lourdes
L
Gutiérrez
Carmen
C
Suárez
Ana
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000908:Antibodies, Fungal / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D015415:Biomarkers; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D015995:Prevalence; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000908:Antibodies, Fungal; D015415:Biomarkers; D007070:Immunoglobulin A; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10