The Effect of Tolerance to Noninherited Maternal HLA Antigens on the Survival of Renal Transplants from Sibling Donors

Burlingham, William J.; Grailer, Alan P.; Heisey, Dennis M.; Claas, Frans H.J.; Norman, Douglas J.; Mohanakumar, T.; Brennan, Daniel C.; Fijter, Hans de; Gelder, Teun van; Pirsch, John D.; Sollinger, Hans W.; Bean, Michael A.

doi:10.1056/nejm199812033392302

Cited by 253 publications

(151 citation statements)

References 27 publications

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“…Confrontation of the fetal/newborn immune system with the NIMA may have a lifelong influence on the immune response of the child. It has been shown in transplantation studies, that haplo-identical NIMA-mismatched sibling transplants had a graft survival similar to that of HLA-identical siblings, whereas NIPA-mismatched sibling transplants did as poorly as did recipients of maternal and paternal grafts (9).…”

mentioning

confidence: 99%

Protective effect of noninherited maternal HLA-DR antigens on rheumatoid arthritis development

Feitsma

Worthington

Mil

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Rheumatoid arthritis (RA) is a complex genetic disorder in which the HLA-region contributes most to the genetic risk. HLA-DRB1-molecules containing the amino acid sequence DERAA (i.e., HLA-DRB1*0103, *0402, *1102, *1103, *1301, *1302, and *1304) are associated with protection from RA. It has been proposed that not only inherited but also noninherited HLA-antigens from the mother (NIMA) can influence RA-susceptibility. Up to now, no protective NIMAs were described. Here, we studied whether DERAA-containing HLA-DRB1-alleles as NIMA are associated with a protective effect. One hundred seventy-nine families were studied, 88 from the Netherlands and 91 from the United Kingdom. The frequency of DERAA-containing HLA-DRB1-alleles of the Dutch mothers (16.1%), but not of the fathers (26.2%), was lower compared with the general Dutch population (29.3%; P ‫؍‬ 0.02). This was replicated in the English set of patients and controls (P ‫؍‬ 0.01). Further, of all families, 45 contained at least one DERAAnegative child with RA and at least one DERAA-positive parent. The odds for the DERAA-negative RA patients of having a DERAApositive mother was significantly lower compared with having a DERAA-positive father (OR 0.25; P ‫؍‬ 0.003). These data show a protective NIMA-effect in a human autoimmune disease and indicate that a DERAA-positive mother can transfer protection against RA to her DERAA-negative child.autoimmunity ͉ DERAA ͉ NIMA

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confidence: 99%

Protective effect of noninherited maternal HLA-DR antigens on rheumatoid arthritis development

Feitsma

Worthington

Mil

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Although cellular components of the maternal and fetal immune systems are generally separated by the placenta, compelling evidence indicates a bidirectional transfer of maternal and fetal cells during gestation. For example, long-term effects of noninherited maternal antigens (NIMA) on immune programing have been well documented (18,19). Furthermore, several lines of evidence support the notion of fetal and newborn immune imprinting.…”

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confidence: 99%

Protective Role of Passively Transferred Maternal Cytokines against Bordetella pertussis Infection in Newborn Piglets

et al. 2017

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Maternal vaccination represents a potential strategy to protect both the mother and the offspring against life-threatening infections. This protective role has mainly been associated with antibodies, but the role of cell-mediated immunity, in particular passively transferred cytokines, is not well understood. Here, using a pertussis model, we have demonstrated that immunization of pregnant sows with heat-inactivated bacteria leads to induction of a wide range of cytokines (e.g., tumor necrosis factor alpha [TNF-␣], gamma interferon [IFN-␥], interleukin-6 [IL-6], IL-8, and IL-12/IL-23p40) in addition to pertussis-specific antibodies. These cytokines can be detected in the sera and colostrum/milk of vaccinated sows and subsequently were detected at significant levels in the serum and bronchoalveolar lavage fluid of piglets born to vaccinated sows together with pertussis-specific antibodies. In contrast, active vaccination of newborn piglets with heat-inactivated bacteria induced high levels of specific IgG and IgA but no cytokines. Although the levels of antibodies in vaccinated piglets were comparable to those of passively transferred antibodies, no protection against Bordetella pertussis infection was observed. Thus, our results demonstrate that a combination of passively transferred cytokines and antibodies is crucial for disease protection. The presence of passively transferred cytokines/antibodies influences the cytokine secretion ability of splenocytes in the neonate, which provides novel evidence that maternal immunization can influence the newborn's cytokine milieu and may impact immune cell differentiation (e.g., Th1/Th2 phenotype). Therefore, these maternally derived cytokines may play an essential role both as mediators of early defense against infections and possibly as modulators of the immune repertoire of the offspring.

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“…Tolerance to NIMA HLA is not restricted to the humoral arm of the immune response. Transplant recipients of a kidney from a one haplotype matched sibling donor are mismatched for either NIMA or NIPA HLA antigens; those patients whose mismatch is for NIMA experience significantly increased graft survival when compared with ones whose mismatch is for NIPA [3]. Finally, cell-mediated, graft-versus-host disease after bone marrow transplant is significantly reduced in recipients of NIMA mismatched as compared with NIPA-mismatched stem cells [4].…”

Section: Introductionmentioning

confidence: 99%

HLA class I noninherited maternal antigens in cord blood and breast milk

Molitor

Haynes²,

Jankowska‐Gan³

et al. 2004

Human Immunology

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The Effect of Tolerance to Noninherited Maternal HLA Antigens on the Survival of Renal Transplants from Sibling Donors

Abstract: In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is higher when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipient.

Cited by 253 publications

References 27 publications

Protective effect of noninherited maternal HLA-DR antigens on rheumatoid arthritis development

Protective effect of noninherited maternal HLA-DR antigens on rheumatoid arthritis development

Protective Role of Passively Transferred Maternal Cytokines against Bordetella pertussis Infection in Newborn Piglets

HLA class I noninherited maternal antigens in cord blood and breast milk

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