Age related alterations in monocytes and T lymphocytes in Specific Polysaccharide Antibody Deficiency (SPAD) Patients may impact on their capacity to respond to Streptococcus pneumoniae

CONSTANZA OTERO; DAMASIA DÍAZ; DANIELA DI GIOVANI; ANDREA GÓMEZ RACCIO; MARTA FINIASZ; GOLDSTEIN DE FINK S; LILIANA BEZRODNIK

Santiago

Congreso; . III LASID (Sociedad Latinoamericana de Inmunodeficiencias); 2013

Sociedad Latinoamericana de Inmunodeficiencias

Introduction: SPAD patients (P) have an abnormal or absent response to polysaccharide antigens and suffer recurrent infections with encapsulated bacteria, like Streptococcuspneumoniae (Spn), but a molecular defect has not yet been found in them yet. In other Primary Immunodeficiencies alterations in monocytes (Mo), dendritic cells and T cells (Tcs) have been reported. Human Mo modulate Tcs to a Th1/Th17 response when challenged with Spn. Objective: to study the immune response to Spn in pediatric P, evaluating effector and memory leukocyte subpopulations from peripheral blood mononuclear cells (PBMC). Methods: The ratio of Mo subsets and naïve or memory Tcs was evaluated at 0h. PBMC were incubated for 48h with heat inactivated Spn (ATCC 49619) to assess cytokine production in CD4 Tcs. All cells were labeled with the corresponding antibodies for flow cytometry analysis with FCS Express Software. Data were statistically analyzed with GraphPad Prism 5.0. We studied 18 P and 20 healthy controls (H). Data were expressed as mean ± SE. Results: In H, we observed an age dependent increase of CD14++CD16- Mo (p= 0.05) and a decrease in CD14++CD16+ Mo (p= 0.05) that was absent in P (Table). In H we observed an age related increase in CD27+CD45RO+ memory Tcs (p= 0.05) and a decrease in CD27+CD45RA+ naïve Tcs (p= 0.05) that was not observed in P. We observed an increase in IL-9+ CD4 Tcs (p= 0.05) in response to Spn in the older group of P, but not in H; we found no significant differences for IL17+ and IFN-γ+ CD4 Tcs in P and in H. In some P we observed a correlation between low serum IgM and a high percentage of CD14++CD16+ Mo (p<0.01, R2=0.86). Changes in monocyte subpopulations in H and P children % Mo  0hs H  (07-13) H (14-19) P (07-13)  P (14-19) CD14++CD16- 52.64 ± 9.01  89.79 ± 1.34*  76.30 ± 76.30  80.02 ± 5.25 CD14++CD16+  39.83 ± 9.69  6.97 ± 1.35*  15.32 ± 3.67 19.19 ± 4.58 CD14+CD16+  3.96 ± 0.61 3.11 ± 0.33 6.52 ± 1.23  5.65 ± 1.07 Conclusions: Snapper et al proposed that during infections with encapsulated bacteria, polysaccharide-specific (PS) IgG responses depend on CD4 Tcs. They reported in a mouse model that inflammatory Mo induce a PS antibody response to intact Spn. Our results suggest that the immune deficiency in P is more complex than what has been described up to now. Altered ratios of Mo subsets may have an impact on T cell differentiation. It may also be associated to an altered PS antibody production.