Abstract
Therapeutic Immunoglobulin Intravenous (IVIg), approved to treat a wide range of autoimmune and primary immunodeficiency diseases, contain mixture of polyreactive and polyclonal IgG purified from the pooled plasma of thousands of donors. The aim of this study is to characterize the profiles of anti- Human Leukocyte Antigen (HLA) class-I and class-II IgG antibodies in four lots of Moroccan IVIg preparations using Luminex Multiplex Single Antigen Bead Immunoassay and to compare it with the unique high frequency HLA types found in the Moroccan population. Anti-HLA class I IgG profiles were assessed using regular (Labscreen) Beads and iBeads. The regular beads are coated with all conformational and structural variants of HLA-I (HLA heavy chain (HC) with β2-microglobulin (β2m) with or without peptides, β2m-free HC with or without peptides or HC only), quite contrast to iBeads, which contained only native tissue-associated HLA HC with β2m and with or without peptides. The level of antibodies was measured as Mean Fluorescent Intensity (MFI). The reactivity of anti-HLA-I IgG antibodies to different alleles of HLA-I loci differed in their recognition of native HLA-I and other structural variants of the HLA-I. High MFI IgG antibodies in the IVIg corresponded with several high frequency HLA-I alleles (B*0801, B*5001, Cw*0602 and Cw*0702) and HLA-II haplotypes (DQA1*0201-DQB1*0201/DRB1*0301), which accounted for 50% of the total gene frequencies in the Moroccan population. HLA-I reactivity of the IVIg with iBeads confirms that the IgG reacting to normal tissue associated with peptide -associated or -free β2mHC. These findings caution the use of high dose IVIg for the carriers of the high frequency HLA types for it may cause tissue injury. The β2m-free-HC reactivity of IVIg indicates the potential of IVIg to bind to activated T and B cells that express these variants, to suppress antibody production. Such an immunomodulation by IVIg renders benefit for patients with autoimmune diseases and organ transplantation.
Highlights
When Immunoglobulin (Ig) therapy was replaced by Intravenous Immunoglobulin (IVIg) with sera derived from multiethnic population from Morocco, the IVIg was not affordable for most patients, until the Blood Transfusion and Hematology National Center and Fractionation and Biotechnologies French Laboratory (LFB-France) industry subcontracted IVIg production using plasma from MoroccanFatiha EL Hilali et al.: Characterization of the Anti-Human Leukocyte Antigen (HLA) Class I and II IgG Antibodies in Moroccan IVIg UsingRegular Beads and Ibeads in Luminex Multiplex Single Antigen Immunoassay blood donors [1], which included both allo-immunized and non-alloimmunized males and females
Four lots Moroccan IVIg preparations purified from pooled plasma of males and females of different ethnic groups and origins from different parts of the country were tested for reactivity to HLA-I, HLA-II and albumin using
HLA-I and HLA-II reactive high Mean Fluorescent Intensity (MFI) IgG antibodies in the Moroccan IVIg corresponded with several high frequency HLA-I alleles (B*0801, B*5001, Cw*0602 and Cw*0702) and HLA-II haplotypes (DQA1*0201-DQB1*0201/DRB1*0301), which accounted for 50% of the total gene frequencies in the Moroccan population
Summary
When Immunoglobulin (Ig) therapy was replaced by Intravenous Immunoglobulin (IVIg) with sera derived from multiethnic population from Morocco, the IVIg was not affordable for most patients, until the Blood Transfusion and Hematology National Center and Fractionation and Biotechnologies French Laboratory (LFB-France) industry subcontracted IVIg production using plasma from MoroccanFatiha EL Hilali et al.: Characterization of the Anti-HLA Class I and II IgG Antibodies in Moroccan IVIg UsingRegular Beads and Ibeads in Luminex Multiplex Single Antigen Immunoassay blood donors [1], which included both allo-immunized and non-alloimmunized males and females. When Immunoglobulin (Ig) therapy was replaced by Intravenous Immunoglobulin (IVIg) with sera derived from multiethnic population from Morocco, the IVIg was not affordable for most patients, until the Blood Transfusion and Hematology National Center and Fractionation and Biotechnologies French Laboratory (LFB-France) industry subcontracted IVIg production using plasma from Moroccan. Fatiha EL Hilali et al.: Characterization of the Anti-HLA Class I and II IgG Antibodies in Moroccan IVIg Using. Moroccan IVIg therapy is administered to primary deficiency, autoimmune and neurological diseases, including. Very little effort has been made to characterize the composition of Moroccan IVIg, pooled and purified from the plasma of Moroccan population, which has remarkable ethnic and genomic diversities, which is reflected in their Human. 2017, it has been reported that the Human major histocompatibility complex includes highly polymorphic proteins of classical HLA class I Studies examining HLA-I types in Casablanca, the largest region of Morocco, reported that the most frequent types were HLA-
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