Analysis of Specific IgG Titers Against Tick-Borne Encephalitis in Patients with Primary Antibody Deficiency Under Immunoglobulin Substitution Therapy: Impact of Plasma Donor Origin

Abstract

Immunoglobulin (Ig) replacement therapy is effective in reducing infections in patients with primary antibody deficiency (PAD). Diversity of specific antibodies is achieved by pooling plasma from over 1000 donors usually of a given geographic region. However, there is no agreement with regard to an optimal vaccination schedule for plasma donors. Especially for tick-borne encephalitis (TBE), regional vaccination rates differ widely among populations due to the epidemiology of the disease. We analyzed specific antibody titers against TBE in comparison to total IgG levels in 162 serum samples collected from 110 PAD patients substituted with polyvalent intravenous IgG or subcutaneous IgG. Some patients received different IgG products over time leading to a total number of 122 different patient-IgG product combinations. Positive TBE-specific IgG levels were detected in 35 cases when measured by standard ELISA and could be confirmed by demonstration of neutralizing antibodies in 31 cases. The detection of specific antibody levels correlated with the geographic origin of the IgG preparations. No titers were detectable in patients substituted with IgG products from North-American donors, whereas variable degrees of anti-TBE titers were observed in patients receiving products from different European countries. We suggest considering the patients’ personal risk for TBE when selecting an appropriate Ig preparation. These data support regional plasma donation in order to address the diverse local infection profile.

Characterization of antibodies in human immunoglobulin products from different regions worldwide

“…Globally, the IVIG samples analyzed showed significant levels of antibodies against most of the studied pathogens, although differences associated with the geographic origin of the pooled plasma were observed. This confirms the existence of unique properties in the plasma source of the IVIGs (Rabel et al, 2012;Goldacker et al, 2014;Planitzer et al, 2011a;Audet et al, 2006;Weeke-Luttmann et al, 1984, Nobre et al, 2014. Hence, IVIG lots from Australia and Canada showed the highest titers for 13 of the 24 pathogens studied, most of them including globally distributed viruses (e.g., IBV, PIV, B19, and EBV) (Pison, 2019), and viruses influenced by the local vaccination programs (e.g., MSLV, RUBV, PV1, and MUMV (Young et al, 2017a;Young et al, 2017b Macartney et al, 2017;Farcet et al, 2019).…”

“…This confirms the existence of unique properties in the plasma source of the IVIGs. [14] , [15] , [16] , [17] , [18] , [35] Hence, IVIG lots from Australia and Canada showed the highest titer in 13 of the 24 pathogens studied, most of them including globally distributed viruses (e.g., IBV, PIV, B19, and EBV), 39 and viruses influenced by the local vaccination programs (e.g., MSLV, RUBV, PV1, and MUMV [40] , [41] , [42] , [43] , [44] ). Australia and Canada, together with the United States, include communities with the highest standard of living in our list, 21 which showed high titers against (PIV, IBV and EBV).…”

“…Depending on the geographic area where the donor population lives, differences in antibody profiles in manufactured IVIG have been reported. [14] , [15] , [16] , [17] , [18] For instance, the immune status of the plasma donors, influenced by community vaccination programs and pathogen exposure, may be responsible for the antibody level variability in IgG preparations from different geographical areas. Commercial IVIG manufacturing usually implies the fractionation of large plasma pools from healthy donors.…”

“…Depending on the geographical area where the donor population lives, differences in antibody profiles in manufactured IVIG have been reported (Rabel et al, 2012;Goldacker et al, 2014;Planitzer et al, 2011a;Audet et al, 2006;Weeke-Luttmann et al, 1984). For instance, the immune status of plasma donors, influenced by community vaccination programs and pathogen exposure, may be responsible for the antibody level variability in IgG preparations from different geographical areas.…”

Editorial: Immunoglobulin Therapy in the 21st Century – the Dark Side of the Moon

“…The final component of this Research Topic of Frontiers in Immunology examines the manufacture of IG therapies and its effect on the efficacy and safety of the products. Goldacker et al ( 22 ) show that, despite the mandatory large plasma donation pool size for IG products, the content of specific, therapeutically important antibodies is still subject to geographical influence. This is very important in the context of continuing to ensure that IG therapies are relevant in the protection of PID patients in different countries.…”