{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:52:15Z","timestamp":1784227935509,"version":"3.55.0"},"reference-count":0,"publisher":"American Diabetes Association","issue":"5","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1991,5,1]]},"abstract":"<jats:p>The onset of insulin-dependent (type I) diabetes is predictable before hyperglycemia by the presence of islet cell autoantibodies (ICAs) and competitive insulin autoantibodies (CIAAs). CIAA+ICA+ first-degree relatives of individuals with type I diabetes have increased numbers of CD4 cells bearing the CD45R antigen and reciprocal depressions of the CD4 cells bearing the CD29 determinant. In addition, depressed CD4\/CD8 ratios are present. In this study, we investigated the correlation between autoantibody levels and T-lymphocyte changes in the prediabetic state. The data demonstrate a clear linear relationship between rising CIAA levels, a marker of disease rate, and rising elevations in the CD4+CD45R+\/CD4+CD29+ ratio in 37 CIAA+ICA+ and CIAA+ICA\u2212 relatives (r = 0.93). In marked contrast, the degree of CD4\/CD8 depression found in individuals with prediabetes or long-term diabetes failed to correlate with either CIAA (r = 0.32) or ICA (r = 0.29) levels. The investigation of T-lymphocyte changes in siblings of individuals with type I diabetes with different stable autoantibody patterns (CIAAs and\/or ICAs), and thus varying risks for diabetes, revealed differences in the prediabetic groups. Fifteen CIAA+ICA\u2212 relatives with high CIAA levels (&amp;gt;80 nU\/ml) had high CD4+CD45R+\/CD4+CD29+ ratios (P = 0.03) and depressed CD4\/CD8 ratios (P = 0.008). In contrast, CIAA+ICA\u2212 relatives with low CIAA levels (39\u201380 nU\/ml), and thus low risk of diabetes, had no alteration in their CD4\/CD8 ratio (P = 0.75) or CD4+CD45R+\/CD4+CD29+ ratio (P = 0.33). Nineteen CIAA\u2212ICA+ siblings with a predicted intermediate risk for diabetes showed heterogeneity in the presence of T-lymphocyte abnormalities. No statistically significant trend was observed in the peripheral T-lymphocyte composition with all CIAA\u2212ICA+ relatives combined. This study links the magnitude of the well-described CIAA production to the magnitude of altered numbers of T lymphocytes bearing the CD45R+ and CD29+ antigens in the prediabetic stage. We conclude that prediabetic relatives prone to frank hyperglycemia represent a heterogeneous population now definable by autoantibody production and the newly described T-lymphocyte changes. This study represents an initial delineation of a link between abnormal alterations in the humoral and cellular immune response.<\/jats:p>","DOI":"10.2337\/diab.40.5.590","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T17:22:06Z","timestamp":1379611326000},"page":"590-597","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":15,"title":["T-Lymphocyte Changes Linked to Autoantibodies: Association of Insulin Autoantibodies With CD4+CD45R+ Lymphocyte Subpopulation in Prediabetic Subjects"],"prefix":"10.2337","volume":"40","author":[{"given":"Denise","family":"Faustman","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital-East, Diabetes Unit, and Massachusetts General Hospital Biostatistics Center, Harvard Medical School\u2008Charlestown; and Joslin Diabetes Center, Harvard Medical School\u2008Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Schoenfeld","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital-East, Diabetes Unit, and Massachusetts General Hospital Biostatistics Center, Harvard Medical School\u2008Charlestown; and Joslin Diabetes Center, Harvard Medical School\u2008Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital-East, Diabetes Unit, and Massachusetts General Hospital Biostatistics Center, Harvard Medical School\u2008Charlestown; and Joslin Diabetes Center, Harvard Medical School\u2008Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/40\/5\/590\/336605\/40-5-590.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/40\/5\/590\/336605\/40-5-590.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:18:43Z","timestamp":1667405923000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/40\/5\/590\/7665\/T-Lymphocyte-Changes-Linked-to-Autoantibodies"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,5,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1991,5,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diab.40.5.590","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,5,1]]}}}