High Titer Anti-Basement Membrane Antibodies in a Subset of Patients with Pediatric Systemic Lupus Erythematosus

Abstract

Background/Aims: There is a critical need for more noninvasive biomarkers to identify nephritis in patients with systemic lupus erythematosus (SLE). Recent studies in a model mouse and an adult SLE patient cohort suggest that anti-basement membrane antibody levels correlate well with lupus activity and kidney injury. The purpose of this study was to assess the anti-basement membrane reactivity in pediatric SLE (pSLE) patients with or without nephritis. Methods: Auto-antibodies to basement membrane antigens were assessed using an anti-matrigel ELISA. Endpoint titers were measured in pSLE patients and healthy children, as well as in autoimmune and non-immune mice, with good reproducing capabilities. Findings were also analyzed with respect to the presence or absence of nephritis, dsDNA antibodies, and other manifestations of pSLE. Results: MRL/lpr mice developed high-titer anti-matrigel antibodies, whereas C57BL/6 mice did not. In a cohort of 21 pSLE patients and 22 pediatric controls, high-titer anti-matrigel IgG, IgM and IgA antibody levels were specific for pSLE. High-titer anti-matrigel IgG3 levels could distinguish with good sensitivity the 13 pSLE patients with a history of nephritis from the 8 non-renal pSLE patients. High-titer anti-matrigel IgG, IgA, IgM or IgG3 did not correlate with positive anti-double stranded DNA, but defined an overlapping subset of patients. Conclusion: The addition of anti-basement membrane antibody testing to serologic testing in pSLE may help to monitor disease activity or to define important subsets of patients with risks for specific disease manifestations.

Novel biomarkers for the assessment of paediatric systemic lupus erythematosus nephritis

“…In one adult study, the serum anti‐GBM has been related to the presence of LN and its activity . In the paediatric population, in a cohort of 21 patients with pSLE the serum anti‐GBM levels could distinguish the 13 pSLE patients with a history of nephritis from the 8 non‐renal pSLE patients . The present study has also verified this observation.…”

Classical complement pathway activation in the nasal tissue of patients with chronic rhinosinusitis

“…Anti-Matrigel antibodies have been studied in SLE since Matrigel® contains many of the constituent matrix proteins that make up basement membranes. (28) We found markedly high levels of anti-Matrigel autoreactive antibodies present in NP tissue that were not detected at higher levels systemically (Fig. 7).…”

“…(34) Basement membrane reactivity was assessed using an ELISA to detect anti-Matrigel matrix antibodies. (28) Matrigel matrix is a reconstituted basement membrane preparation that is extracted from the Engelbreth-Holm-Swarm mouse sarcoma, a tumor rich in extracellular matrix protein. Antibodies were purified from NP tissue extracts and compared with serum from the same CRSwNP patients, along with a random set of serum from control patients.…”

“…Matrigel ELISA was adapted from Orjuela, A. et al(28) Microtiter 96 well plates were coated with 50µl of 500µg/µl of Matrigel® matrix (BD Biosciences) in cold PBS and incubated overnight at 4°C. The plates were washed and blocked with 200µl of PBS containing 3% bovine serum albumin for one hour at room temperature.…”

Η Σημασία Νεότερων Βιολογικών Δεικτών Στην Εκτίμηση Της Νεφρίτιδας Του Νεανικού Συστηματικού Ερυθηματώδους Λύκου

“…[349][350][351] Όσον αφορά τα αντι-GBM, στη μοναδική, πλην της παρούσας, μελέτη που διερεύνησε τη σχέση τους με τα αντι-dsDNA σε παιδιατρικούς ασθενείς, παρατηρήθηκε ότι μεταξύ των ασθενών με υψηλά επίπεδα αντι-GBM, ο αριθμός των ασθενών με θετικά αντι-dsDNA δεν διέφερε σημαντικά από τον αριθμό των ασθενών με αρνητικά αντι-dsDNA. 439 Στην εν λόγω μελέτη συμμετείχαν 21 ασθενείς με πΣΕΛ από τις ΗΠΑ. Σχετικά με την HMGB1, τα αποτελέσματα της παρούσας μελέτης συμφωνούν με αυτά μελέτης με 19 ασθενείς με πΣΕΛ από την Κροατία.…”