title: Increases in circulating and lymphoid tissue interleukin-10 in autoimmune lymphoproliferative syndrome are associated with disease expression.
abstract: Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which genetic defects in proteins that mediate lymphocyte apoptosis, most often Fas, are associated with enlargement of lymph nodes and the spleen and a variety of autoimmune manifestations. Some patients with ALPS have relatives with these same apoptotic defects, however, who are clinically well. This study showed that the circulating levels of interleukin 10 (IL-10) were significantly higher (P <.001) in 21 patients with ALPS than in healthy controls. Moreover, the peripheral blood mononuclear cells (PBMCs) and lymphoid tissues of these patients with ALPS contained significantly higher levels of IL-10 messenger RNA (mRNA; P <.001 and P <.01, respectively). By fractionating PBMC populations, disproportionately high concentrations of IL-10 mRNA were found in the CD4(-)CD8(-) T-cell population, expansion of which is virtually pathognomonic for ALPS. Immunohistochemical staining showed intense IL-10 protein signals in lymph node regions known to contain CD4(-)CD8(-) T cells. Nonetheless, in vitro studies showed no influence of IL-10 on the survival of CD4(-)CD8(-) T cells. Overexpression of IL-10 in patients with inherited apoptotic defects is strongly associated with the overt manifestations of ALPS.
authors.affiliation: Laboratory of Clinical Investigation, Clinical Research Training Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: U
authors.initials: U
authors.lastname: Lopatin
authors.forename: X
authors.initials: X
authors.lastname: Yao
authors.forename: R K
authors.initials: RK
authors.lastname: Williams
authors.forename: J J
authors.initials: JJ
authors.lastname: Bleesing
authors.forename: J K
authors.initials: JK
authors.lastname: Dale
authors.forename: D
authors.initials: D
authors.lastname: Wong
authors.forename: J
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: S
authors.initials: S
authors.lastname: Fritz
authors.forename: M R
authors.initials: MR
authors.lastname: Morrow
authors.forename: I
authors.initials: I
authors.lastname: Fuss
authors.forename: M C
authors.initials: MC
authors.lastname: Sneller
authors.forename: M
authors.initials: M
authors.lastname: Raffeld
authors.forename: T A
authors.initials: TA
authors.lastname: Fleisher
authors.forename: J M
authors.initials: JM
authors.lastname: Puck
authors.forename: W
authors.initials: W
authors.lastname: Strober
authors.forename: E S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: S E
authors.initials: SE
authors.lastname: Straus
mesh_terms: D017209:Apoptosis; D001327:Autoimmune Diseases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008221:Lymphoid Tissue / Q000378:metabolism*; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008297:Male; D012333:RNA, Messenger / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D012333:RNA, Messenger; D016753:Interleukin-10