Non-responsiveness to hepatitis-B vaccination: Revaccination and immunogenetic typing

Krämer, Alexander; Herth, D.; Keyserlingk, H. von; Ludwig, William; Hampl, H.; Sommer, D.; Hahn, Eckhart G.; Riecken, Ernst–Otto

doi:10.1007/bf01726924

Cited by 7 publications

(6 citation statements)

References 20 publications

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“…This association was confirmed in healthy persons by Craven et al [5] but was not observed in further studies [4,7,8]. The strongest association with a low humoral immune response to hepatitis B vaccine was found with the DR3 aUele in healthy persons [2][3][4]6] and in haemodialysis patients [7,8]. The differences between responders and non-responders in the incidence of this allele, however, were markedly lower in the previous studies as compared to our present work.…”

Section: Discussionsupporting

confidence: 77%

“…Some data on the influence of the presence or association between HLA aUeles and the immune response to absence of certain MHC class I, II and III aUeles on the hepatitis B immunization. These studies were performed either in healthy persons [2][3][4][5][6] or in end-stage renal disease (ESRD) patients [4,7,8]. The risk of acquiring hepatitis B infection of these patients is high especially following haemodialysis treatment, therefore immunization with hepatitis B vaccine is highly recommended.…”

Section: Judit Kramer Phd National Institute Of Haematology Blood Tmentioning

confidence: 99%

See 1 more Smart Citation

Relationship Between the Reactivity to Hepatitis B Virus Vaccination and the Frequency of MHC Class I, II and III Alleles in Haemodialysis Patients

et al. 1995

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To study the immunoreactivity genes in a heterogeneous human population needs a large number of individuals. Associations between HLA antigens and immunoresponse to viral or bacterial antigens have been studied with controversial results. As a homogeneous population, the MHC class I, II and III allele distribution was studied in 153 end-stage renal disease patients (ESRD, average duration of renal replacement: 8.2 + 5.1 years) immunized with a recombinant hepatitis B vaccine in accordance to the standard vaccination schedule. Thirty-four patients with an antibody titre of less than 10 U/l following the last booster injection were considered as non-responders while 119 patients with antibody titre equal to or more than 10 U/l were considered as responders. The responder group was divided into two subgroups: low responders (antibody titre: < or = 1000 U/l) and high responders (antibody titre: > 1000 U/1). Marked differences were observed between responders and non-responders in the occurrence of carriers of different MHC class I, II and III alleles. Homozygotes for HLA-A1, HLA-B8, HLA-DR3 and HLA-DQ2 were found almost exclusively in the non-responder group and significantly more heterozygotes for these alleles were found in the non-responder group compared to the responders. Similar albeit less marked differences were found in the frequency of some MHC class III alleles (C4A*6, C4A*QO, Bf*F, Bf*S0.7). Within the responder group, carriers of HLA-A2, HLA-B7 and HLA-DR4 were found to be clustered in the low responder sub-group whereas carriers of HLA-A1, HLA-B27, HLA-Cw2, C4A*6 and Bf*F were observed more frequently in the group of high responders. Similar differences were found with extended haplotypes as well. For example, the extended haplotypes HLA-A1, B8, BfS, C4AQO, C4B1, DR3, DQ2 and HLA-A1, B8, BfF, C4A6, C4B2, DR3, DQ2 were present in nine of 34 cases of non-responders but only in one of 119 case of responders (P < 0.000001). These observations indicate that the presence or absence of certain MHC alleles even in heterozygous form determine the responsiveness to hepatitis B vaccination in end-stage renal disease patients, and among responders, the intensity of antibody response is also markedly influence by immunogenetic factors.

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Section: Discussionsupporting

confidence: 77%

Section: Judit Kramer Phd National Institute Of Haematology Blood Tmentioning

confidence: 99%

Relationship Between the Reactivity to Hepatitis B Virus Vaccination and the Frequency of MHC Class I, II and III Alleles in Haemodialysis Patients

et al. 1995

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“…transforming growth factor-[, leukotrienes, prostaglandins-E, TNF-00 may suppress antigen-induced T lymphocyte proliferation. 31,2,6 Using flow cytometry methods, quantitative determination of monocyte phagocytosis was possible.…”

Section: Discussionmentioning

confidence: 99%

Defective antigen presentation by monocytes in ESRD patients not responding to hepatitis B vaccination: impaired HBsAg internalization and expression of ICAM‐1 and HLA‐DR/Ia molecules

Stachowski

Barth²,

Pollok³

et al. 1995

Mediators of Inflammation

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This study was undertaken to evaluate the monocyte function of uraemic non-responders to hepatitis B vaccination. Therefore, some parameters concerning antigen processing by monocytes (Mo) as antigen presenting cells (APC) were analysed. It was found that in uraemic non-responders, (1) the internalization of HBsAg by monocytes was significantly decreasjed—HBsAg complexed with specific IgG or as immune complex isolated from patients is better internalized compared with free HBsAg; (2) during antigen presentation the expression of adhesion (ICAM-1) and accessory (HLA-DR/Ia) molecules was significantly decreased in uraemic patients, especially in non-responders; and (3) impaired internalization of HBsAg as well as a decrease in ICAM-1 and HLA-DR/Ia expression, correlated well with the blunted proliferation of CD4+ T cells stimulated by autologous monocytes induced by HBsAg.

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“…Despite these impediments, we have recently demonstrated that the human antibody response to immunization with the HBsAg vaccine is MHC associated. Many clinical studies have demonstrated that up to 7.5% of otherwise healthy HBsAg vaccine recipients are poor or nonresponders (5)(6)(7)(8)(9)(10)(11). In our initial study of a group of such nonresponders, we noted an increased incidence of individuals presumably homozygous (by phenotype) for the HLA class I gene HLA-B8, the class II gene HLA-DIL3, and the genes for the complement proteins BF*S, C2"C, C4A*QO (a null gene), and C4B'1 (12).…”

mentioning

confidence: 99%

The immune response to hepatitis B vaccine in humans: inheritance patterns in families.

Kruskall

Alper

Awdeh

et al. 1992

The Journal of Experimental Medicine

135

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Sl~1"EllrlaryWe have recently shown that the human antibody response to the hepatitis B virus surface antigen (HBsAg) vaccine is major histocompatibility complex (MHC) associated. In studies of nonresponders to the vaccine, we found an increased incidence of individuals homozygous for human histocompatibility leukocyte antigen (HLA) proteins associated with the extended (conserved) haplotype SC01,DR3]. In later prospective vaccination trials, we showed that none of five individuals homozygous for this haplotype developed more than 1,300 radioimmunoassay (RIA) units of antibody (mean, 467 RIA units), while all heterozygotes made at least 2,500 RIA units (mean antibody level, 15,608 units). Our results suggested that [HLA-B8,SC01,DR3] lacks an immune response gene for HBsAg, and that response is inherited in a dominant fashion. To provide further evidence for this hypothesis, we have now analyzed the results of HBsAg immunization in families. 43 members of 10 families were immunized with the hepatitis B vaccine, including seven families where at least one member bore the haplotype [HLA-BS,SC01,DR3], and three families where one member had already received, but failed to respond to, the vaccine. In two of these three families, the presence of [HLA-BS,SC01,DR3] was subsequently found. Of nine MHC-identical sibling pairs in the study, both members of eight pairs had similar antibody responses (five nonresponder and three responder pairs). In all families with such sibling pairs, including the discordant pair, rank-ordering members by antibody level demonstrated that no relative's value came between the sibling pair values. Furthermore, of nine [HLA-BS,SC01,DR3]-haplotypehomozygous individuals, six were nonresponders, and two others had only low-normal responses.[HLA-BS,SC01,DR3]-heterozygous family members always had higher levels of antibody than their homozygous relatives. Linkage analysis of nonresponse to HLA haplotypes revealed a maximum likelihood LOD (logarithm of the odds) score of 6.3 at a recombination fraction of 0.1. The MHC association with lack of antibody response to HBsAg was not seen with tetanus immunization, where 1 of 20 HBsAg responders and 1 of 21 poor or nonresponders had tetanus titers of <1:512; both tetanus nonresponders were [HLA-B8,SC01,DR3] heterozygotes. Our results indicate that: (a) response to the HBsAg vaccine is MHC linked, and inherited in a dominant fashion; (b) an abnormal or missing immune response (Ir) gene for HBsAg is a characteristic of most examples of the extended haplotype [HLA-B8,SC01,DR3]; and (c) other haplotypes also have abnormal or missing Ir genes for HBsAg.

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Non-responsiveness to hepatitis-B vaccination: Revaccination and immunogenetic typing

Cited by 7 publications

References 20 publications

Relationship Between the Reactivity to Hepatitis B Virus Vaccination and the Frequency of MHC Class I, II and III Alleles in Haemodialysis Patients

Relationship Between the Reactivity to Hepatitis B Virus Vaccination and the Frequency of MHC Class I, II and III Alleles in Haemodialysis Patients

Defective antigen presentation by monocytes in ESRD patients not responding to hepatitis B vaccination: impaired HBsAg internalization and expression of ICAM‐1 and HLA‐DR/Ia molecules

The immune response to hepatitis B vaccine in humans: inheritance patterns in families.

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