The Urine of SLE Patients Contains Antibodies that Bind to the Laminin Component of the Extracellular Matrix

Ben‐Yehuda, Arie; Rasooly, Linda; a, Ruth Bar-Tan; Breuer, Gabriel S.; Tadmor, Boaz; Ulmansky, Rina; Naparstek, Yaakov

doi:10.1006/jaut.1995.0021

Cited by 47 publications

(40 citation statements)

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“…However, both antia-actinin and antilaminin antibodies have been never be documented in the kidney of human LN and data of the literature indicate that both proteins cross-react with anti-DNA antibodies. 38,40 Therefore, additional studies must address the role of anti-a-actinin and antilaminin antibodies before concluding on this aspect. A special focus of our study was a-enolase, because its serum levels are very high (in the range of 40-50 mg/L, with peaks up to 300 mg).…”

Section: Discussionmentioning

confidence: 99%

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo

Bruschi¹,

Sinico

Moroni

et al. 2014

Journal of the American Society of Nephrology

100

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Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against a-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of a-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti-a-enolase (.15 mg/L) IgG2 and/or anti-annexin AI (.2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti-a-enolase/low anti-annexin AI IgG2 and patients with low anti-a-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti-a-enolase IgG2 recognized specific epitopes of a-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human a-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against a-enolase and annexin AI predominate in the glomerulus and can be detected in serum.

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Section: Discussionmentioning

confidence: 99%

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo

Bruschi¹,

Sinico

Moroni

et al. 2014

Journal of the American Society of Nephrology

100

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“…Many of the self-Ags among this highly reactive set are known to be associated with various autoimmune diseases such as myelin oligodendrocyte glycoprotein with multiple sclerosis (53,103); MIF and CA125 with rheumatoid arthritis (104); glucagon with type 1 diabetes (105); and Laminin, low-density lipoprotein, and high-density lipoprotein with systemic lupus erythematosus (106,107). Thus, the prevalence of some autoimmune diseases may be associated with the underlying prevalence in health of some autoantibody specificities; autoimmune disease, then, can be related to the loss of healthy regulation rather than to the accidental emergence of a forbidden clone (108).…”

Section: Discussionmentioning

confidence: 99%

Tumor-Associated and Disease-Associated Autoantibody Repertoires in Healthy Colostrum and Maternal and Newborn Cord Sera

Madi

Bransburg-Zabary

Maayan-Metzger

et al. 2015

The Journal of Immunology

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In this work, we studied autoantibody repertoires and Ig isotypes in 71 mothers and their 104 healthy newborns (including twins and triplets delivered term or premature). Newborns receive maternal IgG Abs via the placenta before birth, but developing infants must produce their own IgM and IgA Abs. We used an Ag microarray analysis to detect binding to a selection of 295 self-Ags, compared with 27 standard foreign Ags. The magnitude of binding to specific self-Ags was found to be not less than that to the foreign Ags. As expected, each newborn shared with its mother a similar IgG repertoire—manifest as early as the 24th week of gestation. IgM and IgA autoantibody repertoires in cord sera were highly correlated among the newborns and differed from their mothers’ repertoires; the latter differed in sera and milk. The autoantibodies bound to self-Ags known to be associated with tumors and to autoimmune diseases. Thus, autoantibody repertoires in healthy humans—the immunological homunculus—arise congenitally, differ in maternal milk and sera, and mark the potential of the immune system to attack tumors, beneficially, or healthy tissues, harmfully; regulation of the tissue site, the dynamics, and the response phenotype of homuncular autoimmunity very likely affects health.

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“…The titers of either anti-ECM or antilaminin urinary Abs correlated with SLE disease activity (7). Analysis of the ␣1 laminin component revealed that the lupus Abs bind to the E3 C-terminal constituent of the ␣1 laminin chain (data not shown).…”

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confidence: 93%

Treatment with a Laminin-Derived Peptide Suppresses Lupus Nephritis

Amital

Heilweil

Ulmansky

et al. 2005

The Journal of Immunology

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The role of DNA as the target for pathogenic lupus autoantibodies in systemic lupus erythematosus is equivocal and renal damage may be due to cross-reactivity of lupus Abs with glomerular components. We have previously shown that lupus autoantibodies bind to the laminin component of the extracellular matrix. In the present work, we have analyzed the fine specificity of the interaction of pathogenic murine lupus autoantibodies with this molecule and the effect of inhibiting their binding to laminin during the course of the disease. We have found that pathogenic murine lupus autoantibodies react with a 21-mer peptide located in the globular part of the α-chain of laminin. Immunization of young lupus-prone mice with this peptide accelerated renal disease. Analysis of transgenic, congenic, and RAG-1−/− mice confirmed the importance of this epitope in the pathogenesis of lupus renal disease. We have synthesized a panel of peptides that cross-react with the anti-laminin Abs and have found that the binding of lupus autoantibodies to the extracellular matrix could be inhibited in vitro by some of these competitive peptides. Treatment of MRL/lpr/lpr mice with these peptides prevented Ab deposition in the kidneys, ameliorated renal disease, and prolonged survival of the peptide-treated mice. We suggest that laminin components can serve as the target for lupus Abs. The interaction with these Ags can explain both the tissue distribution and the immunopathological findings in lupus. Moreover, inhibition of autoantibody binding to the extracellular matrix can lead to suppression of disease.

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The Urine of SLE Patients Contains Antibodies that Bind to the Laminin Component of the Extracellular Matrix

Cited by 47 publications

References 0 publications

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo

Tumor-Associated and Disease-Associated Autoantibody Repertoires in Healthy Colostrum and Maternal and Newborn Cord Sera

Treatment with a Laminin-Derived Peptide Suppresses Lupus Nephritis

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