CD207+/CD1a+ CIRCULATING CELLS ARE PRESENT IN PATIENTS WITH ACTIVE LANGERHANS CELL HISTIOCYTOSIS

NOWAK WANDA; TESSONE LICINA; ESTECHO IVANA G; ARMESTO ARNALDO R; ELENA GRACIELA; CARRERA SILVA EUGENIO A; ROSSO DIEGO A; ERRASTI ANDREA E

Mar del Plata

Congreso; Reunión Conjunta SAIC-SAI-SAFE 2016; 2016

SAIC-SAI-SAFE

<!-- /* Font Definitions */@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536859905 -1073711037 9 0 511 0;}@font-face{font-family:"ＭＳ 明朝";mso-font-charset:78;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1791491579 18 0 131231 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-520092929 1073786111 9 0 415 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;mso-pagination:widow-orphan;font-size:11.0pt;font-family:Calibri;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:ZH-CN;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:11.0pt;mso-ansi-font-size:11.0pt;mso-bidi-font-size:11.0pt;font-family:Calibri;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES;mso-fareast-language:ZH-CN;}.MsoPapDefault{mso-style-type:export-only;margin-bottom:10.0pt;}@page WordSection1{size:8.5in 11.0in;margin:1.0in 1.25in 1.0in 1.25in;mso-header-margin:.5in;mso-footer-margin:.5in;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->Background: Langerhans Cells Histiocytosis (LCH)is a disorder characterized by an abnormal accumulation of CD207+CD1a+myeloid cells in almost any tissue. The precursors of these pathogenic cellswere not yet clearly defined in vivo, however, it has been shown in vitro thatmonocytes and CD1c+ dendritic cells can achieve high levels of CD207and CD1a when exposed to TGFb and TSLP. We hypothesized that precursor cellsexpressing CD207 and/or CD1a should be circulating in active multisystem LCHpatients. Methods: Pediatricpatients with confirmed diagnosis of LCH were stratified as unisystem ormultisystem; unifocal or mutifocal; with active disease (AD) or non-activedisease (NAD). CD1a and CD207 expression was analyzed in blood mononuclearcells of LCH children and compared with same compartment of cells from healthyadults and umbilical cord blood by FACS analysis. Plasma TSLP and TGFb wereanalyzed by ELISA. Results: Themyeloid compartment showed a significant increase of CD11b fraction includingCD11bhigh plus CD11b+ (36.4 ± 3.7, N=11) in AD vs NADpatients (18.9 ± 1.7, N=12) and healthy adults (24.9 ± 1.3, N=12). We have alsoidentified the presence of high percentage of circulating CD11bhighCD11c+CD207+cells (39 ± 9.4, N=12) in AD vs NAD (3.1 ± 0.5, N=11), healthy adults(0.6 ± 0.4, N=9) and umbilical cord blood (2.1 ± 0.5, N=5). Moreover,circulating CD11chighCD207+CD1a+ cells (19 ±7.4, N=12) are present in active multisystem patients compared with NAD (2.1 ±0.4, N=12), healthy adults (0.7 ± 0.3, N=8) and umbilical cord blood (2.8 ± 1.1,N=4). TSLP and TGFb levels were significantly increased in active LCH comparedto non-active patients. Conclusions: Circulatingmonocytes expressing CD207 as well as DCs expressing CD207/CD1a were found in multisystemactive disease. In concordance with this result we observed increased plasmalevels of TSLP and TGFb in active LCH patients suggesting that these cytokinescould be key drivers of pathogenic LC in vivo.