“Natural” Human Leukocyte Antigen Antibodies Found in Nonalloimmunized Healthy Males

Abstract

Normal males were found to have HLA antibodies to infrequent HLA specificities. It is likely that these HLA antibodies are produced to cross-reactive epitopes found in microorganisms, ingested proteins and allergens-making them natural antibodies.

Therapeutic preparations of IVIg contain naturally occurring anti–HLA-E antibodies that react with HLA-Ia (HLA-A/-B/-Cw) alleles

“…The Cw* reactivity of IVIg is comparable to the high incidence of HLA-Ia reactivities found in normal sera. 11 IVIg reacted with several B* alleles, and high reactivity was observed with B*8201, B*1512, and B*4501. The high reactivity of IVIg observed with several B* alleles is also comparable to the incidence of HLA-B reactivity of normal nonalloimmunized male sera.…”

“…The high reactivity of IVIg observed with several B* alleles is also comparable to the incidence of HLA-B reactivity of normal nonalloimmunized male sera. 11 IVIg also reacted strongly with a few A* alleles, including A*8001, A*3401, A*4301, A*6601, and A*6602. Interestingly, the high reactivity of IVIg with these A* alleles is strikingly similar to the high incidence of HLA-A reactivity observed with normal male sera.…”

“…Consequently, it may contain HLA antibodies because several allo-HLA antibodies are known to occur naturally in the sera of both men (nonalloimmunized) and women. [9][10][11][12][13] MoralesBuenrostro et al 11 demonstrated the specificities and incidence of these allo-HLA-I Abs in nonalloimmunized males. Neither the origin nor cause of anti-HLA Abs occurring in healthy individuals has been established.…”

Randomized Controlled Trial of High-Dose Intradermal Versus Standard-Dose Intramuscular Influenza Vaccine in Organ Transplant Recipients

“…Other patients that were newly screen positive displayed nonspecific reactivity but no clear specificity pattern. Nonspecific reactivity can be found commonly in the healthy population (25). In transplantation, one study showed that de novo DSA was seen in up to 15% of kidney transplant patients followed over a mean of 4.6 years (26).…”

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors

“…Previous studies have shown that this sensitive assay employing recombinant HLA antigens can result in a frequent detection of antibodies directed against a limited number of rare HLA antigens in nontransfused males and even in cord blood. 15,16 These antibodies have been termed 'natural antibodies', and the majority of targeted epitopes consist of hidden amino acids that are believed to be inaccessible in the intact form of the HLA antigens. 16 Indeed, natural antibodies detected in renal allograft recipients were not predictive of graft failure.…”