Key Points
Therapeutic preparations of IVIg have high levels of HLA (Ia and Ib) reactivity. Anti–HLA-E mAbs mimicked IVIg HLA-I reactivity. Anti–HLA-E mAbs might be useful in suppressing HLA antibody production similar to IVIg and in the way that anti-RhD Abs suppress production.
Phenotypic expression of human leukocyte antigen (HLA)-E on the surface of tumor lesions includes intact heterodimer [HLA-E heavy chain and b2-microglobulin (b2m)] and b2m-free monomer. Anti-HLA-E monoclonal antibodies (mAbs), MEM-E=02 or 3D12 bind to the peptide sequences in b2m-free HLA-E, which is common and shared with HLA-Ia monomers. A newly developed monospecific anti-HLA-E mAb (TFL-033) recognizes HLA-E-restricted peptide sequences on a1 and a2 helices away from b2-m-site. Tumor progression may involve shedding of b2-m from HLA-E or overexpression of b2m-free monomers. There is a need to identify and distinguish the different phenotypic expression of HLA-E, particularly the intact heterodimer from the b2m-free monomer on the surface of tumor lesions. Because of the unique peptide-binding affinities of the mAbs, it is hypothesized that TFL-033 and MEM-E=02 may distinguish the phenotypic expressions of cell surface HLA-E during stages of tumor progression. Only TFL-033 stained diffusely the cytoplasm of normal mucosa. The incidence and intensity of TFL-033 staining of the cell surface in early stages, poorly or undifferentiated and non-nodal lesions and in diffuse carcinoma is greater than that of MEM-E=02. Whereas MEM-E=02 stained terminal stages, adenocarcinoma and lymph node metastatic lesions intensely, either owing to increased expression of b2m-free HLA-E with tumor progression or owing to expression of HLA-Ia molecules. Our study evaluates the relative diagnostic potential of HLA-E-monospecific TFL-033 and the HLA-Ia-reactive MEM-E=02 for determining the specific distribution and immunodiagnosis of different phenotypic expression HLA-E in tumor lesions, and the structural and functional alterations undergone by HLA-E during tumor progression.Structural and functional alterations of human leukocyte antigens (HLA) are implicated in tumor immune escape. 1 The escape mechanism involves loss or downregulation of classical HLA class I antigens (HLA-A, -B and -C) and=or aberrant overexpression of nonclassical HLA class I antigens (HLA-E and -G). Consequently, these changes in HLA classes lead to decreased recognition or destruction of tumor cells by immune cytotoxic effectors, mainly cytotoxic lymphocytes (CTL) and natural killer T (NKT) cells. 1
Summary
Activated CD4+ T cells undergo blastogenesis and proliferation and they express several surface receptors, including β2-microglobulin-free human leucocyte antigen (
While transplant education disseminated in dialysis centers can increase access to kidney transplant, dialysis-center barriers to transplant are common. Also, little research has examined which specific approaches to transplant education are most effective. To address these gaps, we surveyed transplant educators in 1,694 U.S. dialysis centers about their transplant knowledge, use of 12 specific education practices, and 8 identified barriers to providing education. Transplant wait-listing rates were calculated using data from the USRDS. After categorizing the education practices into combined strategies, 52% of educators orally recommended transplant to patients, 31% had in-center discussions about transplant with patients, 17% distributed print educational resources, and 3% used intensive education approaches. Distribution of print education [Incident rate ratio (IRR): 1.02 1.15 1.30 ] and using >1 intensive education practice (1.00 1.11 1.23) within dialysis centers were associated with increased wait-listing rates. Several dialysis center characteristics were associated with reduced odds of using education strategies leading to increased wait-listing. Centers with greater percentages of patients without health insurance in the zip code [Odds ratio (OR): 0.96 0.97 0.99 ], in rural locations (OR: 3 0.66 0.79 0.95), with for-profit ownership (OR: 0.64 0.77 0.91), and with greater percentages of patients older than 65 years (OR: 0.05 0.11 0.23) had lower odds of recommending transplant to patients, while centers with a higher patient-to-staff ratio were more likely to do so (OR: 1.01 1.03 1.04). Language barriers (OR: 0.48 0.64 0.86) and having competing work priorities (OR: 0.40 0.53 0.70) reduced the odds of distributing print education. Providers with greater transplant knowledge were more likely to use >1 intensive educational strategy (OR: 1.01 1.27 1.60) while providers who reported competing work priorities (OR: 0.51 0.66 0.84) and poor communication with transplant centers (OR: 0.58 0.76 0.98) were less likely to use intensive education strategies. With the many challenges of delivering transplant education in dialysis centers, educators should prioritize education strategies shown to be associated with increasing wait-listing rates.
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