{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:08:56Z","timestamp":1791295736086,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,4,7]],"date-time":"2008-04-07T00:00:00Z","timestamp":1207526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>A proportion of HIV patients beginning antiretroviral therapy (ART) develop immune restoration disease (IRD). Immunological characteristics of IRD were investigated in a cohort of HIV patients beginning therapy in Kuala Lumpur, Malaysia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood mononuclear cells were collected at weeks 0, 6, 12, 24 and 48 of ART from five patients experiencing IRD [two with cryptococcal and three with <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (Mtb) disease], eight non\u2010IRD controls who had begun ART with CD4 T\u2010cell counts of &lt;100\u2003cells\/\u03bcL and 17 healthy controls. Leukocytes producing interferon\u2010gamma (IFN\u03b3) were quantified by enzyme\u2010linked immunospot assay after stimulation with purified protein derivative (PPD), early secretory antigenic target\u20106 (ESAT\u20106), <jats:italic>Cryptococcus neoformans<\/jats:italic> or <jats:italic>Cytomegalovirus<\/jats:italic> antigens. Plasma immunoglobulin (IgG) antibodies reactive with these antigens were assessed by enzyme\u2010linked immunosorbent assay. Proportions of activated (HLA\u2010DR<jats:sup>hi<\/jats:sup>) and regulatory (CD25 CD127<jats:sup>lo<\/jats:sup> and CTLA\u20104<jats:sup>+<\/jats:sup>) CD4 T\u2010cells were quantified by flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma HIV RNA declined and CD4 T\u2010cell counts rose within 8\u201327 weeks on ART. Mtb IRD patients displayed elevated IFN\u03b3 responses and\/or plasma IgG to PPD, but none responded to ESAT\u20106. Cryptococcal IRD occurred in patients with low baseline CD4 T\u2010cell counts and involved clear IFN\u03b3 and antibody responses to cryptococcal antigen. Proportions of activated and regulatory CD4 T\u2010cells declined on ART, but remained higher in patients than in healthy controls. At the time of IRD, proportions of activated CD4 T\u2010cells and regulatory CD4 T\u2010cells were generally elevated relative to other patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cryptococcal and Mtb IRD generally coincide with peaks in the proportion of activated T\u2010cells, pathogen\u2010specific IFN\u03b3 responses and reactive plasma IgG. IRD does not reflect a paucity of regulatory CD4 T\u2010cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1468-1293.2008.00565.x","type":"journal-article","created":{"date-parts":[[2008,4,7]],"date-time":"2008-04-07T18:27:42Z","timestamp":1207592862000},"page":"307-316","source":"Crossref","is-referenced-by-count":86,"title":["Immunological profiles of immune restoration disease presenting as mycobacterial lymphadenitis and cryptococcal 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