Both autoantibodies and pathogen-specific antibodies are present in immunoglobulin preparations and reflect characteristics of the donor population

Khan, Sujoy; Sims, Sue; Raine, D; Sewell, William A.

doi:10.1016/j.jaad.2008.07.048

Cited by 6 publications

(7 citation statements)

References 5 publications

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“…One explanation for the seropositive autoantibodies in IVIG against these Ro52, Ro60, La and gastric autoantibodies relates to the large IVIG donor pool who harbor high levels of these autoantibodies because they likely include samples from asymptomatic or pre-symptomatic individuals with autoimmune conditions. Our results and work of others ( 50 ) also suggests that commercial IVIG preparations may differ in autoantibody concentrations due to differences in donor pools and manufacturing. Taken together these results show that IVIG given to MIS-C patients contains a variety of autoantibodies and without testing before IVIG treatment or allowing sufficient time after the dose of IVIG to allow decay of these antibodies before repeat testing, can be mistakenly interpreted as associated with the manifestations of MIS-C. From our analysis of MIS-C IVIG recipients, Ro52, Ro60, and La autoantibodies showed a similar decay profile, in which all three autoantibodies were present in the blood for several weeks before becoming undetectable by 35-60 days.…”

Section: Discussionsupporting

confidence: 75%

Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C

et al. 2022

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The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

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Section: Discussionsupporting

confidence: 75%

Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C

et al. 2022

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“…The high levels of gastric ATPase autoantibodies seen in IVIG are likely due to donors not only having autoimmune gastritis but with other autoimmune diseases including type I diabetes, Sjögren’s syndrome, and SLE in which these antibodies have been detected [56]. Our results and work of others [54] also suggests that commercial IVIG preparations may differ in autoantibody concentrations due to differences in donor pools and manufacturing. Taken together these results show that IVIG given to MIS-C patients contains a variety of autoantibodies and without testing before IVIG treatment or allowing sufficient time after the dose of IVIG to allow decay of these antibodies before repeat testing, can be mistakenly interpreted as associated with the manifestations of MIS-C. Based on our findings, further studies are needed to investigate the nature, prevalence, and possible significance of autoantibody production in MIS-C independently from IVIG administration.…”

Section: Discussionsupporting

confidence: 56%

“…For example, SSA antibody, comprising autoantibodies against Ro52 and Ro60, has previously been detected in IVIG preparations [51], and Ro52 was identified as the most abundant autoantibody present in IVIG preparations used to treat neurological patients [52]. In addition, autoantibodies associated with other autoimmune diseases have been detected in IVIG preparations given to patients, including autoantibodies against GAD65 [53], the acetylcholine receptor [55] and desmosomal proteins [54]. One explanation for the seropositive autoantibodies in IVIG against these Ro52, Ro60, and La relates to the large IVIG donor pool who harbor high levels of these autoantibodies because they likely include samples from asymptomatic or pre-symptomatic individuals with current or future onset of SLE, Sjögren’s syndrome and other autoimmune conditions.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies Detected in MIS-C Patients due to Administration of Intravenous Immunoglobulin

Burbelo

Castagnoli

Shimizu

et al. 2021

Preprint

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The autoantibody profile associated with known autoimmune diseases in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that adults with COVID-19 had a moderate prevalence of autoantibodies against the lung antigen KCNRG, and SLE-associated Smith autoantigen. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Together these findings demonstrate that administration of high-dose IVIG is responsible for the detection of several autoantibodies in MIS-C and KD. Further studies are needed to investigate autoantibody production in MIS-C patients, independently from IVIG administration.

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“…There were marked differences between the native IVIG products with respect to these antibody levels, and their relative order differed between anti‐monomer and anti‐oligomer levels. The issue of variability in specific antibody concentrations between IVIG preparations has been raised by previous investigators [34–36], and may be due to differences in preparation methods and/or donor populations. Because lot‐to‐lot variability for specific antibody levels in IVIG preparations has also been reported [37,38], the possibility cannot be ruled out that the differences we detected in anti‐α‐synuclein antibody levels between IVIG preparations could be due, at least in part, to lot‐to‐lot variation.…”

Section: Discussionmentioning

confidence: 99%

Specific antibodies to soluble alpha-synuclein conformations in intravenous immunoglobulin preparations

Patrias¹,

Klaver²,

Coffey

et al. 2010

Clinical and Experimental Immunology

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SummaryAlpha-synuclein is the major protein in Lewy bodies, the hallmark pathological finding in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Although normally intracellular, it also can be secreted, so extracellular alpha-synuclein may contribute to neuronal injury. Serum antibodies to alpha-synuclein could exert protective effects by increasing alpha-synuclein's movement out of the brain and, if they cross the blood-brain barrier, by inhibiting its neurotoxic effects. The objective of this study was to measure antibody concentrations to alpha-synuclein monomer and soluble oligomers in three intravenous immunoglobulin (IVIG) preparations, Gamunex (Talecris Biotherapeutics), Gammagard (Baxter Healthcare) and Flebogamma (Grifols Biologicals). Antibodies were measured in native IVIG preparations and after antibody-antigen complex dissociation. IVIG's non-specific binding was subtracted from its total binding to alpha-synuclein to calculate specific anti-alpha-synuclein antibody concentrations. Specific antibodies to alphasynuclein monomer and/or soluble oligomers were detected in all IVIG products. In native IVIG preparations, the highest anti-monomer concentrations were in Gammagard and the highest anti-oligomer concentrations were in Gamunex; the extent to which lot-to-lot variation may have contributed to these differences was not determined. Antibody-antigen complex dissociation had variable effects on these antibody levels. The IVIG preparations did not inhibit alpha-synuclein oligomer formation, although they changed the distribution and intensity of some oligomer bands on Western blots. The presence of antibodies to soluble alpha-synuclein conformations in IVIG preparations suggests that their effects should be studied in animal models of synucleinopathies, as a first step to determine their feasibility as a possible treatment for PD and other synucleinopathies.

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Both autoantibodies and pathogen-specific antibodies are present in immunoglobulin preparations and reflect characteristics of the donor population

Cited by 6 publications

References 5 publications

Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C

Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C

Autoantibodies Detected in MIS-C Patients due to Administration of Intravenous Immunoglobulin

Specific antibodies to soluble alpha-synuclein conformations in intravenous immunoglobulin preparations

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