{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:43:23Z","timestamp":1700786603220},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,12,12]],"date-time":"2005-12-12T00:00:00Z","timestamp":1134345600000},"content-version":"vor","delay-in-days":3267,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[1997,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Objective<\/jats:italic>. To characterize immunologic specificity and possible antiidiotype activity of IgG anti\u2010F(ab\u2032)<jats:sub>2<\/jats:sub> in normal subjects as well as in patients with active and inactive systemic lupus erythematosus (SLE).<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>. IgG anti\u2010F(ab\u2032)<jats:sub>2<\/jats:sub> and anti\u2010double\u2010stranded DNA (anti\u2010dsDNA) were affinity isolated from immunoadsorption columns of F(ab\u2032)<jats:sub>2<\/jats:sub> and dsDNA linked to Sepharose 4B. Affinity\u2010purified IgG anti\u2010F(ab\u2032)<jats:sub>2<\/jats:sub> (APAF) and affinity\u2010isolated IgG anti\u2010dsDNA (APAD) were tested by enzyme\u2010linked immunosorbent assay (ELISA) for other cross\u2010reacting specificities including anti\u2010Sm, anti\u2010Sm\/RNP, and anti\u2010 <jats:italic>Crithidia<\/jats:italic> binding. Anti\u2010DNA specificity of APAF and APAD was assayed by S1 nuclease treatment of heat\u2010denatured DNA. Rabbit antiidiotypic antisera were prepared by immunization with APAF and APAD from normal subjects and SLE patients and absorption with insolubilized human Cohn fraction II (Fr II). V<jats:sub>L<\/jats:sub> and V<jats:sub>H<\/jats:sub> regions of 5 monoclonal IgM antibodies with anti\u2010F(ab\u2032)<jats:sub>2<\/jats:sub>\/anti\u2010DNA specificity generated by Epstein\u2010Barr virus B cell stimulation were sequenced by polymerase chain reaction and characterized for V<jats:sub>H<\/jats:sub> and V<jats:sub>L<\/jats:sub> subgroup. APAF and APAD were also examined by high\u2010resolution electron microscopy for possible ring forms indicative of antiidiotypic V\u2010region interactions.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>. APAF from normal subjects, representing 0.08\u20100.18% of serum IgG, showed striking relative concentrations of both anti\u2010F(ab\u2032)<jats:sub>2<\/jats:sub> and anti\u2010DNA, as well as anti\u2010Sm and anti\u2010Sm\/RNP ELISA reactivity. Both APAF and APAD reacting with F(ab\u2032)<jats:sub>2<\/jats:sub> or dsDNA on the ELISA plate could be cross\u2010inhibited by F(ab\u2032)<jats:sub>2<\/jats:sub> or DNA in solution. Anti\u2010DNA reactivity in normal APAF and APAD was much more sensitive to S1 nuclease treatment than similar fractions from SLE patients. Neither APAF nor APAD from controls produced positive antinuclear immunofluorescence or positive <jats:italic>Crithidia<\/jats:italic> staining, whereas these were strongly positive using SLE APAF and APAD. Absorbed rabbit antisera against normal or SLE APAF and APAD showed strong ELISA reactivity against both APAF and APAD, but no residual reactivity with normal Fr II. V<jats:sub>L<\/jats:sub> and V<jats:sub>H<\/jats:sub> sequencing of monoclonal human IgM antibodies showing both anti\u2010F(ab\u2032)<jats:sub>2<\/jats:sub> and anti\u2010DNA reactivity showed relative V<jats:sub>H<\/jats:sub>3, V<jats:italic>k<\/jats:italic>1 or V<jats:sub>H<\/jats:sub>1, V<jats:italic>k<\/jats:italic>3 restriction. No evidence of ring forms or V\u2010region \u201ckissing\u201d dimers was obtained when normal or SLE APAD or APAF was examined by high\u2010resolution electron microscopy.<\/jats:p><jats:p><jats:italic>Conclusion<\/jats:italic>. IgG anti\u2010F(ab\u2032)<jats:sub>2<\/jats:sub> in both normal subjects and SLE patients represents a polyreactive Ig subfraction with concomitant anti\u2010DNA, anti\u2010Sm, and anti\u2010Sm\/RNP specificities. Anti\u2010DNA reactivity in SLE is qualitatively different from that in normal APAD and APAF since normal APAD and APAF anti\u2010DNA is much more sensitive to S1 nuclease digestion of denatured dsDNA. APAF and APAD share distinct V\u2010region antigens which may be related to prominent V<jats:sub>H<\/jats:sub>3 or V<jats:sub>H<\/jats:sub>1 antigenic components. No evidence for in vivo complexing of anti\u2010DNA and anti\u2010F(ab\u2032)<jats:sub>2<\/jats:sub> as ring forms or antiidiotype\u2010IgG complexes was observed during ultrastructural studies. In both normal individuals and SLE patients, APAF may represent a small polyreactive IgG subfraction which also contains antinuclear and anti\u2010DNA specificities.<\/jats:p>","DOI":"10.1002\/art.1780400116","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T12:15:56Z","timestamp":1171455356000},"page":"109-123","source":"Crossref","is-referenced-by-count":7,"title":["Cross\u2010reactivity of human igg anti\u2010F(ab\u2032)<sub>2<\/sub> antibody with DNA and other nuclear antigens"],"prefix":"10.1002","volume":"40","author":[{"suffix":"Jr.","given":"Ralph C.","family":"Williams","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine C.","family":"Malone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Cimbalnik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew 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