Analysis of CIITA encoding AIR-1 gene promoters in insulin-dependent diabetes mellitus and rheumatoid arthritis patients from the northeast of Italy:Absence of sequence variability

Qualitative and/or quantitative alterations in the expression of rho MWC cl ass II molecules affect the onset and maintenance of the immune response an d may be the basis of a wide variety of disease states, such as autoimmunit y and immunodeficiency. CIITA is a major physiological regulator of the expression of MHC class II genes. The availability of CIITA appears generally essential for MHC class II gene expression, and hence its own transcriptional regulatory mechanisms result of fundamental importance For a correct homeostasis of the immune r esponse. Therefore, it is possible to hypothesize that variability at the C IITA-encoding locus, AIR-I, could constitute an additional source of suscep tible traits to autoimmune diseases, Mutations at AIR-1/CIITA promoters cou ld modulate expression of CIITA. Variations in CIITA expression could influ ence the qualitative and quantitative expression of MHC class II molecules at cell surface. We have analyzed sequence variation at AIR-1/CIITA promote rs by PCR-SSCP in 23 IDDM and 30 RA patients compared to a sample of 19 una ffected normal controls and 16 unaffected IDDM family members, for a total of 88 Caucasian subjects from the Northeast of Italy. No sequence differenc e was found at the four AIR-1/CIITA promoters between autoimmune patients a nd normal controls. Moreover, the promoters resulted invariant within the e ntire group of 88 subjects analyzed, comprising patients and controls. This finding suggests a possible selective advantage in maintaining CIITA upstr eam regulatory sequences invariant. (C) American Society for Histocompatibi lity and Immunogenetics, 2000. Published by Elsevier Science Inc.