Indication of Primary Immune Deficiency in Fanconi's Anemia

Abstract

A girl with various congenital malformations developed pancytopenia and hypoplastic bone marrow at the age of 6 year. A chromosome study of lymphocytes showed numerous breaks, gaps and rearrangements, allowing the diagnosis of Fanconi's anemia. Treatment with corticosteroids and splenectomy did not result in hematologic remission. Repeated immunologic studies showed increasingly deficient T cell function as judged by lymphocyte transformation studies and skin test reactivity, whereas T cell number, T/B cell ratio, immunoglobulins, complement factors and neutrophil function were normal. A sever Pneumocystis carinii pneumonitis developed, but was successfully treated with pentamidine, sulfametoxazole with trimetoprim and transfer factor. Improvement of T cell function followed transfer factor therapy. Combined therapy with corticosteroids and androgens caused partial remission of the hematologic abnormalities. The probability of a primary immune deficiency in the patient is discussed.

Allergic and Immunologic Parameters in Patients with Fanconi`s Anemia

“…In keeping with a previous study [8], no abnormalities were found concerning the levels of IgG, IgA or IgM or the production of isohemagglutinins and antipoliovirus or antimeasles antibodies in this series of FA patients. On the other hand, a high proportion of patients presented elevated IgE levels.…”

“…This is thought to be consequent to a high frequency of chromosomal breaks, which predisposes patients with FA to develop immunodeficiencies, similarly to those observed in patients with other chromosomal instability syndromes including Bloom’s syndrome, ataxia-telangiectasia and Nijmegen’s syndrome [7]. Several immunologic abnormalities in FA patients, including those of cell-mediated immune response [8, 9, 10], low production of interleukins 1, 2, 6, γ-interferon and GM-CSF [10, 11, 12, 13], and reduced NK-cell-mediated cytotoxicity [14]have been reported. Few studies have addressed humoral immune responses in FA patients.…”

Impaired Type I IFN-Induced Jak/STAT Signaling in FA-C Cells and Abnormal CD4+ Th Cell Subsets in Fancc−/− Mice

“…Although the extraordinary incidence of certain cancers in FA remains unexplained, the frequency of head and neck and vulvar cancers suggests that the human papillomavirus (HPV) may play a role in certain FA epithelial malignancies, and recent studies confirm this notion (4 -6). These findings are compatible with the view that FA may be characterized by subtle immune defects: a view supported by mounting preliminary studies and FA patient case reports that suggest subtle defects of lymphoid subsets, especially those involved in cell-mediated immunity (7)(8)(9)(10)(11)(12). In addition, FA patients undergoing transplantation suffer higher rates of aspergillus infection, severe graft-vs-host disease, and high levels of graft rejection (13,14).…”

Fanconi's anaemia associated with haemophilia A

“…Frequent infections are part of the symptomatology in Fanconi's anaemia and have been attributed to the granulocytopenia. A recent report describes a case of Fanconi's anaemia with deficiency of T-lymphocytes resulting in deficient cellular immunity (Karup-Pedersen 1977). The proportion of T-lymphocytes in the peripheral blood was slightly decreased in our patient, but the results of the other immunological tests were normal.…”