Symptomatic hypogammaglobulinemia in infancy and childhood – clinical outcome and in vitro immune responses

BACKGROUND: Symptomatic hypogammaglobulinemia in infancy and childhood (SHIC), may be an early manifestation of a primary immunodeficiency or a maturational delay in the normal production of immunoglobulins (Ig). We aimed to evaluate the natural course of SHIC and correlate in vitro lymphoproliferative and secretory responses with recovery of immunoglobulin values and clinical resolution. METHODS: Children, older than 1 year of age, referred to our specialist clinic because of recurrent infections and serum immunoglobulin (Ig) levels 2 SD below the mean for age, were followed for a period of 8 years. Patient with any known familial, clinical or laboratory evidence of cellular immunodeficiency or other immunodeficiency syndromes were excluded from this cohort. Evaluation at 6- to 12-months intervals continued up to 1 year after resolution of symptoms. In a subgroup of patients, in vitro lymphocyte proliferation and Ig secretion in response to mitogens was performed. RESULTS: 32 children, 24 (75%) males, 8 (25%) females, mean age 3.4 years fulfilled the inclusion criteria. Clinical presentation: ENT infections 69%, respiratory 81%, diarrhea 12.5%. During follow-up, 17 (53%) normalized serum Ig levels and were diagnosed as transient hypogammaglobulinemia of infancy (THGI). THGI patients did not differ clinically or demographically from non-transient patients, both having a benign clinical outcome. In vitro Ig secretory responses, were lower in hypogammaglobulinemic, compared to normal children and did not normalize concomitantly with serum Ig's in THGI patients. CONCLUSIONS: The majority of children with SHIC in the first decade of life have THGI. Resolution of symptoms as well as normalization of Ig values may be delayed, but overall the clinical outcome is good and the clinical course benign

Modulation of B and T cell subsets in mice treated with fractionated total lymphoid irradiation (TLI). IV. Expression of TL4-bearing cells in spleen and bone marrow of TLI-treated mice.

Abstract The pre-thymic cell phenotypes arising in spleen and bone marrow (BM) of fractionated total lymphoid irradiation (TLI)-treated mice are characterized in this paper. Different strains of mice received 200 rad lymphoid irradiation daily for 8 to 10 days. At different time intervals after treatment, BM or spleen cells of treated mice were stained with a battery of antisera directed specifically to TL and Thy-1 antigens. Analysis of the stained cells on a fluorescence-activated cell sorter (FACS) apparatus revealed that 10 to 30% of spleen or BM cells of TLI-treated mice were TL+ cells whereas no TL+ cells could be found in the same organs in the normal untreated mice. The appearance of TL+ cells in the spleen and BM of TLI-treated mice was found to be thymic independent, as thymectomy of mice neither prevented nor altered the kinetics of TL+ cell appearance. The sequence of antigenic marker appearance reveals that TL markers precede Thy-1 markers and that TLaa markers precede TL4 antigen. The relevance of the TL4+ cells to the development of leukemias is discussed.</jats:p