HLA class I NK-epitopes and KIR diversities in patients with multiple myeloma

• Published in: Immunogenetics (New York) Vol. 76; no. 3; pp. 155 - 164
• Main Authors: Beelen, Nicky A., Molenbroeck, Stefan J. J., Groeneveld, Lisette, Voorter, Christien E., Bos, Gerard M. J., Wieten, Lotte
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-06-2024; Springer Nature B.V
• Subjects: Allergology; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cell Biology; Disease control; Epitopes; Gene Function; Genotypes; Histocompatibility antigen HLA; Human Genetics; Immunological tolerance; Immunology; Immunosuppression; Killer cell immunoglobulin-like receptors; Malignancy; Multiple myeloma; Natural killer cells; Original; Original Article; Plasma cells; Potassium channels (inwardly-rectifying); Self; Human leukocyte antigen genes; Association; Natural killer cells; Killer-cell immunoglobulin-like receptor; Multiple myeloma
• ISSN: 0093-7711; 1432-1211
• DOI: 10.1007/s00251-024-01336-w

Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion of malignant plasma cells in the bone marrow. Myeloma cells are susceptible to killing by natural killer (NK) cells, but NK cells fail to control disease progression, suggesting immunosuppression. The activation threshold of NK-effector function is regulated by interaction between KIRs and self-HLA class I, during a process called “education” to ensure self-tolerance. NK cells can respond to diseased cells based on the absence of HLA class I expression (“Missing-self” hypothesis). The HLA and KIR repertoire is extremely diverse; thus, the present study aimed to characterize potential variances in genotypic composition of HLA Class I NK-epitopes and KIRs between MM patients and healthy controls. Genotypic expression of KIR and HLA (HLA-C group-C1/C2 and Bw4 motifs (including HLA-A*23, A*24, A*32) were analyzed in 172 MM patients and 195 healthy controls. Compared to healthy controls, we did not observe specific KIR genes or genotypes, or HLA NK-epitopes with higher prevalence among MM patients. The presence of all three HLA NK-epitopes (C1
+
C2
+
Bw4
+
) was not associated with MM occurrence. However, MM patients were more likely to be C1
-
/C2
+
/Bw4
+
(
p
= 0.049, OR 1.996). In line with this, there was a trend of increased genetic co-occurrence of Bw4 and KIR3DL1 in MM patients (
p
= 0.05, OR 1.557). Furthermore, MM patients were more likely to genetically express both C2/KIR2DL1 and Bw4/KIR3DL1 (
p
= 0.019, OR 2.453). Our results reveal an HLA NK-epitope combination that is associated with the occurrence of MM. No specific KIR genotypes were associated with MM.