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CD46 was discovered in 1986 during a search for novel C3b-binding proteins. CD46 is expressed ubiquitously and functions as a co-factor in the factor I-mediated proteolytic cleavage of C3b and C4b. Its vital role in preventing complement deposition on host tissue is underpinned by the fact that deficiency of CD46 is a predisposing factor for numerous disease conditions arising from complement-mediated 'self-attack'. However, in the last 10 years, it has become apparent that CD46 is also heavily involved in a new and somewhat surprising functional aspect of the complement system: the down-modulation of adaptive T helper type 1 (Th1) immune responses by regulating the production of interferon (IFN)-γ versus interleukin (IL)-10 within these cells. Specifically, this latter function of CD46 is a tantalizing discovery - it may not only have delivered the explanation as to why so many pathogens use and abuse CD46 as cell entry receptor but clearly has important clinical implications for the better understanding of Th1-mediated disease states and novel therapeutic approaches for their amelioration. Here, we summarize and discuss the current knowledge about CD46 and its expanding roles in the immune system. [ABSTRACT FROM AUTHOR]

The HPA-15 (Gov) alloantigen is a biallelic co-dominant system on human platelets, and its alleleHPA-15aandHPA-15bdiffer by an A→C single nucleotide polymorphism at nucleotide 2108 of the coding sequence resulting in a Tyr682Ser substitution in the mature CD109 glycoprotein.Employing the polymerase chain reaction-restriction fragment length polymorphism technique, we determined the HPA-15 gene frequencies among 276 subjects of distinct Brazilian ethnic groups including, 15 Caucasians, 15 African Brazilians, 15 Orientals, 106 Amazon Xikrin Indians, 31 Amazon Gaviões Indians and 94 blood donors.The calculatedHPA-15aandHPA-15ballele frequencies found in Caucasians (0.53/0.47), African Brazilians (0.57/0.43), Orientals (0.57/0.43) and Brazilian blood donors (0.52/0.48) did not differ significantly. However, theHPA-15aandHPA-15bgene frequencies of Xikrin Indians (0.78/0.22) were significantly different from that of all other groups (P < 0·01). TheHPA-15a/a,HPA-15a/bandHPA-15b/bgenotype frequencies observed in Gaviões Indians were significantly different from those seen in African Brazilians (P = 0·04) and blood donors (P = 0·017).The present data showed that the distribution of the HPA-15 (Gov) system alleles observed among the Brazilian population is quite similar to the distributions already reported among Asian, Canadian and European populations. Moreover, the data indicated differences in the frequency of the HPA-15 system between Amazon Indians and other distinct Brazilian ethnic groups suggesting that Amerindians would be at higher risk of HPA-15 alloimmunization in the need of receiving blood components collected from blood donors of other ethnic groups. [ABSTRACT FROM AUTHOR]