期刊
TRANSPLANT IMMUNOLOGY
卷 69, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.trim.2021.101465
关键词
Alloantibody desensitization; B cell depletion; Belimumab; Complement C1q; Human leukocyte antigen; Kidney transplantation; Immunosuppression; IgG antibody; BLyS; BAFF and APRIL
In highly sensitized kidney transplant candidates, BLyS blockade did not significantly reduce total anti-HLA allo-Ab levels but resulted in selective depletion of antibodies recognizing specific HLA allele specificities.
Pre-existing anti-HLA allo-antibodies (allo-Abs) are a major barrier to successful kidney transplantation, resulting in an elevated risk for antibody-mediated rejection (AMR) and eventual graft loss. The cytokine B lymphocyte stimulator (BLyS) promotes B cell maturation and plasma cell survival; consequently, anti-BLyS therapy represents a potential therapeutic opportunity in diminishing pre-existing allo-Abs. Here we report that in our 1-year pilot trial, BLyS neutralization failed to reduce total anti-HLA allo-Ab levels in highly sensitized candidates awaiting kidney transplant in a clinically meaningful way. Additionally, we performed a post hoc analysis using sera from trial candidates which revealed selective depletion of anti-HLA class I and class II Abs in response to belimumab treatment, restricted to certain allele specificities and IgG subclasses. Altogether, we observed that BLyS blockade only results in selective depletion of anti-HLA Abs recognizing a few discrete HLA allele specificities.
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