Anti-GalNAcβ: A novel anti-glycan autoantibody associated with pregnancy loss in women with antiphospholipid syndrome and in a mouse experimental model

Blank, Miri; Krause, Ilan; Dotan, Nir; Anafi, Liat; Eisenstein, Miriam; Cervera, Ricard; Meroni, Pier Luigi; Shoenfeld, Yehuda

doi:10.1016/j.jaut.2012.07.002

Cited by 8 publications

(4 citation statements)

References 47 publications

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“…Monach and colleagues (15) have recently reported that IgG fractions purified from joint immune complexes bound a diverse subset of proteins and peptides from synovium and cartilage. Elevations of a variety of antiglycan Abs, including IgG, IgA, IgE, and IgM classes, have been demonstrated in a number of inflammatory autoimmune diseases (16)(17)(18)(19). However, of studies on the diagnostic value, Ag specificity, and pathogenic potential of autoantibodies correlated to the development of RA in humans, very few touched upon glycanspecific autoantibodies (20)(21)(22), even though carbohydrate structures represent a substantial portion of tissue Ags in the joints and could be targeted, just like any other autoantigens, by arthritogenic autoantibodies.…”

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confidence: 99%

Disease Association and Arthritogenic Potential of Circulating Antibodies against the α1,4-Polygalacturonic Acid Moiety

Dai

Dong

Gong

et al. 2014

The Journal of Immunology

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Much progress has been made in recent years on the diagnostic value, Ag specificity, and pathogenic roles of autoantibodies correlated to the development of rheumatoid arthritis (RA) in humans. However, carbohydrate Ag-specific autoantibodies that may also play important roles in RA have largely been ignored. In this article, we report that serum levels of Abs capable of recognizing α1,4-polygalacturonic acid [(PGA); major structural component of pectin] strongly correlate with RA in humans. The measurements of PGA-specific Abs (PGA-Abs) in sera are comparable to rheumatoid factors and anti–cyclic citrullinated peptide Abs as serological diagnostic markers for RA in terms of sensitivity and specificity. Immunohistochemical staining results indicate that the PGA-Abs selectively bound synovial membrane cells and chondrocytes in the joints of both humans and rabbits (but not rodents). Induction of PGA-Abs by s.c. immunization of rabbits with carrier protein–conjugated synthetic PGA led to severe inflammatory reactions (synovial hyperplasia, small vessel proliferation, and inflammatory cell infiltration) in the joints. Injection of affinity purified anti-PGA IgG into the synovial cavity of rabbits resulted in accumulation of proinflammatory cytokines such as TNF-α, IL-8, and IL-1β in synovial fluid, as well as local pathological damage. We conclude that the PGA–cross-reactive moiety represents a major autoantigen in the joints and can be targeted by autoantibodies capable of triggering arthritogenic responses in vivo.

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confidence: 99%

Disease Association and Arthritogenic Potential of Circulating Antibodies against the α1,4-Polygalacturonic Acid Moiety

Dai

Dong

Gong

et al. 2014

The Journal of Immunology

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“…The model was consistent with previous ones showing that i.p. injections of human IgG with aPL activity to pregnant naïve mice after embryo implantation or treatment with antibiotics was able to modulate inflammatory cascade at the placental level affecting the fetal resorption rate or growth retardation …”

Section: Discussionmentioning

confidence: 99%

Human IgG Antinuclear Antibodies Induce Pregnancy Loss in Mice by Increasing Immune Complex Deposition in Placental Tissue:In VivoStudy

Veglia

D’Ippolito

Marana

et al. 2015

Am J Reprod Immunol

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“…A pivotal feature of RM is the response of auto-antibodies to different auto-antigens (3). Auto-antibodies toward laminin-1 (4) and GalNAcβ determinant of glycans have been detected in women with RM (5). Anti-phospholipid syndrome with anti-cardiolipin or lupus anticoagulant antibodies is present in 15% of women with the recurrent first and second trimester miscarriage (2,6).…”

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confidence: 99%

“…Sinсе the mаternаl immune response toward the fetus is associated with secondary infertility, it is important to search for novel auto-antigens that could contribute to the recurrent pregnancy losses. Although auto-antibodies have been proposed as an etiology of RM (2,5), the mechanisms leading to antibody development and targets of these auto-antibodies are poorly understood. Recently, we have detected higher levels of IgGs tightly bound to chorionic tissue of RM patients in comparison to findings from the embryonic kidney, lung, heart, intestine, and skin of a spontaneously aborted fetus due to other etiology (7).…”

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confidence: 99%

Detection of novel auto-antigens in patients with recurrent miscarriage: description of an approach and preliminary findings

et al. 2014

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AimTo develop and test a protocol for isolation of potential auto-antigens from chorionic tissue that may be linked to recurrent miscarriage (RM).MethodsThe strategy included: 1) isolation of IgGs tightly bound to chorionic tissue of RM patients by protein G chromatography; 2) construction of affinity columns using the chorionic antibodies for isolation of auto-antigens; 3) enrichment of auto-antigens from detergent extracted solution of chorionic proteins by affinity chromatography; 4) separation by dodecyl sulfate-electrophoresis followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry identification.ResultsFive potential auto-antigens were detected: neutral alpha-glucosidase AB, endoplasmin, transitional endoplasmic reticulum ATPase, putative endoplasmin-like protein, and cytoplasmic actin 2.ConclusionsWe developed a strategy for identification of auto-antigens in the chorionic tissue of women with RM, which could be of diagnostic and prognostic value.

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Anti-GalNAcβ: A novel anti-glycan autoantibody associated with pregnancy loss in women with antiphospholipid syndrome and in a mouse experimental model

Cited by 8 publications

References 47 publications

Disease Association and Arthritogenic Potential of Circulating Antibodies against the α1,4-Polygalacturonic Acid Moiety

Disease Association and Arthritogenic Potential of Circulating Antibodies against the α1,4-Polygalacturonic Acid Moiety

Human IgG Antinuclear Antibodies Induce Pregnancy Loss in Mice by Increasing Immune Complex Deposition in Placental Tissue:In VivoStudy

Detection of novel auto-antigens in patients with recurrent miscarriage: description of an approach and preliminary findings

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