Additional file 1 of Effects of uric acid-lowering therapy (ULT) on renal outcomes in CKD patients with asymptomatic hyperuricemia: a systematic review and meta-analysis

Additional file 1: Supplementary Figure 1. Assessment of the methodological quality of the included studies. (A) Risk of Bias (B) Risk of Bias Summary

Anti-Neu5Gc and anti-non-Neu5Gc antibodies in healthy humans

<div><p>Our group previously investigated the levels of anti-Gal and anti-nonGal IgM and IgG in a cohort of 75 healthy humans of various backgrounds, and found some significant differences related to factors such as age, gender, ABO blood group, diet, vaccination history, and geographic location during childhood. We have now expanded our cohort (n = 84) to investigate the levels of anti-Neu5Gc and anti-nonGal/nonNeu5Gc antibodies in healthy humans. Anti-nonGal and anti-nonGal/nonNeu5Gc human IgM and IgG binding to pRBCs and pAECs from GTKO/CD46 and GTKO/CD46/Neu5GcKO pigs were measured by flow cytometry. Anti-Gal and anti-Neu5Gc IgM and IgG levels were measured by ELISA. In summary, (i) the great majority (almost 100%) of humans had anti-Neu5Gc IgM and IgG antibodies that bound to p<u>AECs</u> and approximately 50% had anti-Neu5Gc antibodies that bound to p<u>RBCs</u>, (ii) there was significantly less human antibody binding to pig cells that did not express either Gal or Neu5Gc compared with those that did not express Gal alone, (iii) the levels of both IgM and IgG binding to GTKO/CD46/Neu5GcKO p<u>RBCs</u> and p<u>AECs</u> were low, (iv) the level of anti-Neu5Gc IgG was higher in men than women, (v) the level did not change with age or diet, and there was some variability associated with (vi) previous vaccination history and (vii) the geographic region in which the individual spent his or her childhood. Our study confirms that human antibody binding to <u>RBCs</u> and <u>AECs</u> from GTKO/CD46/Neu5GcKO pigs is greatly reduced compared to binding to GTKO/CD46 cells. However, all humans appear to have a low level of antibody that binds to p<u>AECs</u> that is not directed to either Gal or Neu5Gc. Our findings require consideration in planning clinical trials of xenotransplantation.</p></div

Correlation of human serum anti-Neu5Gc IgM and IgG antibodies with vaccination history.

<p>Correlation of human serum anti-Neu5Gc IgM and IgG antibodies with vaccination history.</p

Incidence (and percentage) of human serum IgM and IgG antibodies binding to pRBCs and pAECs.

<p>Incidence (and percentage) of human serum IgM and IgG antibodies binding to pRBCs and pAECs.</p

Definitions of anti-pig IgM and IgG antibodies.

<p>Anti-pig antibodies (both IgM and IgG) such as anti-Gal, anti-Neu5Gc, anti-nonGal, and anti-nonGal/nonNeu5Gc were defined according to binding to various pig cells.</p

Age, gender, ABO group, dietary and vaccination histories, and geographic area of childhood in 84 healthy human subjects from whom sera were studied in the present report.

<p>Age, gender, ABO group, dietary and vaccination histories, and geographic area of childhood in 84 healthy human subjects from whom sera were studied in the present report.</p

Expression of Gal, Neu5Gc, and hCD46 on wild-type, GTKO/CD46, GTKO/CD46/Neu5GcKO pig and human RBCs and AECs by flow cytometry.

<p>RBCs and AECs from GTKO/CD46 pigs expressed Neu5Gc, but not Gal. AECs from these pigs expressed hCD46, but RBCs did not. Neither Gal nor Neu5Gc was expressed on GTKO/CD46/Neu5GcKO pig RBCs or AECs. Human AECs expressed hCD46, but not Gal or Neu5Gc.</p