Renal Transplant Patients Biopsied for Cause and Tested for C4d, DSA, and IgG Subclasses and C1q: Which Humoral Markers Improve Diagnosis and Outcomes?

Abstract

The association between donor specific antibodies (DSA) and renal transplant rejection has been generally established, but there are cases when a DSA is present without rejection. We examined 73 renal transplant recipients biopsied for transplant dysfunction with DSA test results available: 23 patients diffusely positive for C4d (C4d+), 25 patients focally positive for C4d, and 25 patients negative for C4d (C4d−). We performed C1q and IgG subclass testing in our DSA+ and C4d+ patient group. Graft outcomes were determined for the C4d+ group. All 23 C4d+ patients had IgG DSA with an average of 12,500 MFI (cumulative DSA MFI). The C4d− patients had average DSA less than 500 MFI. Among the patients with C4d+ biopsies, 100% had IgG DSA, 70% had C1q+ DSA, and 83% had complement fixing IgG subclass antibodies. Interestingly, IgG4 was seen in 10 of the 23 recipients' sera, but always along with complement fixing IgG1, and we have previously seen excellent function in patients when IgG4 DSA exists alone. Cumulative DSA above 10,000 MFI were associated with C4d deposition and complement fixation. There was no significant correlation between graft loss and C1q positivity, and IgG subclass analysis seemed to be a better correlate for complement fixing antibodies in the C4d+ patient group.

Protective Effects of Ophiocordyceps lanpingensis on Glycerol-Induced Acute Renal Failure in Mice

“…IgG is one of the critical substances in the immune system of the body, which is synthesized and secreted by plasma cells in spleen and lymph nodes. IgG plays an important role in the immune and physiological adjustment [ 39 , 40 ]. As the main antibody composition in the serum, IgG is widely distributed in tissues, which possesses anti-infection function.…”

IgG4 donor-specific HLA antibody profile is associated with subclinical rejection in stable pediatric liver recipients

“…Patients with detectable class II DSA, compared to those without, had a higher median (interquartile range) total class II eplet mismatch (33 vs 26 ) and HLA-DQ alone mismatch (12 [8][9][10][11][12][13][14][15][16] vs 8 [4][5][6][7][8][9][10][11][12][13][14][15]). Similarly, total class II eplet mismatch was higher for those with MFI sum >20 000 vs ≤20 000 (40 [28-51] vs 28 [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]). Among subjects with class II DSA, total class II eplet mismatch was higher for those with maximum MFI > 20 000 vs ≤20 000 (39 vs 30 [21][22][23][24][25][26][27][28][29][30]…”

“…Among subjects with class II DSA, total class II eplet mismatch was higher for those with maximum MFI > 20 000 vs ≤20 000 (39 [25-53] vs 30 [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]). Similarly, total class II eplet mismatch was higher for those with MFI sum >20 000 vs ≤20 000 (40 [28-51] vs 28 [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]). To further explore DSA attributes, which may aid in cluster prediction, we interrogated IgG subclass composition.…”

Technical challenges and clinical relevance of single antigen bead C1q/C3d testing and IgG subclass analysis of human leukocyte antigen antibodies

“…Therefore, modified SAB assays measuring C1q binding to HLA antibodies or C3d deposition on beads have been introduced in recent years . In addition, several research groups have modified SAB assays in order to be able to analyze the IgG subclass distribution of HLA antibodies .…”

“…With a lack of standardized tests, several groups modified the luminex IgG SAB assay in order to gain insight into the IgG subclass distribution of serum HLA antibodies simply by replacing the polyclonal pan‐IgG detection antibody with IgG subclass detection antibodies . While the end concentrations of the detection antibodies in different studies vary from 0.25 to 20 μg/ml, lack of appropriate controls to determine the specificity of these detection antibodies might have resulted in overestimated results because of the crossreactivity between different subclasses .…”