Should mild hypogammaglobulinemia be managed as severe hypogammaglobulinemia? A study of 389 patients with secondary hypogammaglobulinemia.

BACKGROUND: Although secondary hypogammaglobulinemia is more frequent than primary hypogammaglobulinemia, its etiology and management are poorly described, particularly for mild hypogammaglobulinemia. METHODS: This retrospective observational study included all adult patients with a gammaglobulin level <6.4g/L on serum electrophoresis identified at Dijon teaching hospital between April and September 2012. Clinico-biological features, etiologies and infectious complications were collected at inclusion and compared between group 1 (gammaglobulin <5g/L, severe hypogammaglobulinemia), and group 2 (gammaglobulin <6.4 and ≥5g/L, mild hypogammaglobulinemia). RESULTS: Among the 4011 serum electrophoreses, 570 samples from 389 patients had gammaglobulin levels below 6.4g/L: 156 (40%) in group 1 and 233 (60%) in group 2. Mean age±SD was 67 (15) years, and sex ratio was 1.04 (M/F) with no difference between the two groups. An etiology was identified in 79% and 58% of patients in groups 1 and 2, respectively (p<0.0001). The main etiologies were similar in both groups and included malignant hemopathy treated with cytostatic agents (n=129, 33%), smoldering or newly-diagnosed hemopathy without treatment (n=49, 13%) and immunosuppressive treatment (n=91, 23%). The incidence of hypogammaglobulinemia-related infections was 22/100/year, with no significant difference between the two groups (p=0.17). Vaccination coverage against pneumococcus was 33%, and higher in group 1 (46% vs. 24%; p<0.0001). When no cause was known at inclusion, an etiology was discovered in 22/130 patients (17%), 11 in each group. CONCLUSIONS: Though mild hypogammaglobulinemia does not meet the classical criteria for hypogammaglobulinemia (<5g/L), the etiology and infectious risk are similar. It therefore requires investigation and vaccination.

Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis.

OBJECTIVE: Giant cell arteritis (GCA) is the most frequently occurring vasculitis in elderly individuals, and its pathogenesis is not fully understood. The objective of this study was to decipher the role of the major CD4+ T cell subsets in GCA and its rheumatologic form, polymyalgia rheumatica (PMR). METHODS: A prospective study of the phenotype and the function of major CD4+ T cell subsets (Th1, Th17, and Treg cells) was performed in 34 untreated patients with GCA or PMR, in comparison with 31 healthy control subjects and with the 27 treated patients who remained after the 7 others withdrew. RESULTS: Compared with control subjects, patients with GCA and patients with PMR had a decreased frequency of Treg cells and Th1 cells, whereas the percentage of Th17 cells was significantly increased. Furthermore, an analysis of temporal artery biopsy specimens obtained from patients affected by GCA for whom biopsy results were positive demonstrated massive infiltration by Th17 and Th1 lymphocytes without any Treg cells. After glucocorticoid treatment, the percentages of circulating Th1 and Th17 cells decreased, whereas no change in the Treg cell frequency was observed. The frequency of CD161+CD4+ T cells, which are considered to be Th17 cell precursors, was similar in patients and control subjects. However, these cells highly infiltrated GCA temporal artery biopsy specimens, and their ability to produce interleukin-17 in vitro was significantly enhanced in patients with GCA and patients with PMR and was correlated with a decrease in the phosphorylated form of STAT-1. CONCLUSION: This study is the first to demonstrate that the frequency of Treg cells is decreased in patients with GCA and patients with PMR, and that CD161+CD4+ T lymphocytes, differentiated into Th1 cells and Th17 cells, are involved in the pathogenesis of GCA and PMR.