Anwar Sheikha

Circulating levels of cytokines and soluble cytokine receptors in various T‐cell malignancies

Background. Cytokines, interleukin (IL)‐4, IL‐6, interferon‐gamma (IFN‐γ), tumor necrosis factor‐alpha (TNF‐α), soluble CD23 (sCD23), and soluble IL‐2 receptors (sIL‐2R) are mediators of inflammation and immune response. Alterations in immune status of patients with various cancers may result in release of cytokines in circulation. The authors measured the circulating levels of IL‐4, IL‐6, IFN‐γ TNF‐α, sCD23, and sIL‐2R from patients with T‐cell chronic lymphocytic leukemia (T‐CLL), T‐cell acute lymphoblastic leukemia (T‐ALL) and peripheral T‐cell lymphoma (PTCL) to determine their importance in these T‐cell disorders.

Otological manifestations of thalassaemia intermedia: evidence of temporal bone involvement and report of a unique cholesteatoma-like lesion

Thalassaemia intermedia should be considered in any chronically anaemic patient presenting from the Middle East with hearing impairment. We report here three Saudi siblings with thalassaemia intermedia and features of severe bone marrow expansion, particularly invading the temporal bone. They were seen first for their otological problems before they had access to proper haematological evaluation. One member was admitted for surgical exploration of a cholesteatoma, which was then found to be marrow expansion of the temporal bone. Screening of the family revealed two more anaemic siblings with thalassaemia intermedia. Audiological examination of all the family members showed that only the two affected members had a high frequency sensori-neural hearing loss. Bone marrow expansion into the temporal bone is a rare feature of thalassaemia intermedia. Cholesteatoma-like lesion has not been previously described. It has to be considered in all cases of symptomatic thalassaemia intermedia manifesting with cavitation and lytic lesions in the mastoid system. The likelihood that sensorineural hearing loss may complicate the thalassaemias is raised and the possible mechanism for such involvement discussed. The proper management for different otological manifestations of the thalassaemias is suggested. These cases would suggest a more extensive involvement of the temporal bone in the thalassaemias than has been previously recognized. Further large scale studies are required to illuminate the subject.

Peripheral T‐cell lymphomas. Immunoregulatory cytokine (interleukin‐2, interleukin‐4, and interferon‐gamma) abnormalities and autologous mixed lymphocyte reaction

Background. Cytokines are the most important secretions of the immune system and have a wide range of immunoregulatory functions in various immune disorders and T‐cell malignancy. The authors have determined that characteristic enhanced autologous mixed lymphocyte reaction (AMLR) of the lymph node‐derived malignant T‐cells from peripheral T‐cell lymphomas is a function of the T‐cell derived cytokines interleukin (IL) 2, IL‐4, and interferon‐gamma (IFN‐τ).

Peripheral T-cell lymphoma with unique immunologic features.

Background. The autologous mixed lymphocyte reaction (AMLR) is an important immunoregulatory phenomenon in human immune disorders. The authors have determined the phenotype and assessed the response of malignant lymph node T‐cells, from histologically and immunologically proven cases of peripheral T‐cell lymphoma, in AMLR and allogeneic mixed lymphocyte reaction (MLR) and studied the secretion of lymphokines.

Phenotypic and functional T cell subset abnormalities in patients with aplastic anaemia and hypogammaglobulinaemia

We have investigated T cell abnormalities present in blood of two patients with aplastic anaemia and hypogammaglobulinaemia. There was a marked increase in class II. major histocompatibility complex, HLA‐DR+ antigen, and interleukin‐2 receptor (Tac+) bearing CD4+ helper/inducer T cells, and a concurrent reduction of CD8+ suppressor/cytotoxic T cells. These CD4+ T cells produced an elevated proliferative response to phytohaemagglutinin and concanavalin A. Interestingly, the T cell subset mainly responsible for elevated production of the lymphokine, interkeukin‐2, under the stimulus of phytohaemagglutinin, was characterized as belonging to a CD4+ T cell subset. Functional studies, using a pokeweed mitogen driven IgG, IgA and IgM synthesis, demonstrated a correlation between CD4+ T cell deficient helper function for B cell differentiation and the clinical finding of the patients hypogammaglobulinaemia.

Regulation of interleukin-4 production and cytokine-induced growth potential in peripheral T-cell non-Hodgkin's lymphomas

The malignant cells in tumour tissues produce cytokines/growth factors that may influence tumour growth, tumour immunogenicity and host immune response. We demonstrate that lymph node cell (LNC) purified neoplastic T cells from CD4+ peripheral T‐cell lymphoma (CD4+ PTCL) and CD8+ PTCL spontaneously, and after stimulation with anti‐CD3, secreted high amounts of interleukin‐4 (IL‐4) as compared to LNC‐purified CD4+ and CD8+ non‐malignant T cells. Furthermore, IL‐4 was observed to be the most potent cytokine that induced in vitro proliferation and growth of the malignant T cells. Moreover, malignant T‐cell‐derived IL‐4 secretion was augmented by exogeneous recombinant human interferon‐gamma (IFN‐γ) and was profoundly inhibited by IL‐2. Because IL‐4 was shown to be a locally active cytokine with a wide range of immunoregulatory properties, regulation of IL‐4 production by IFN‐γ and IL‐2 in malignant T cells may be one of the important parameters to be assessed in the design of anticancer‐specific immunotherapy. In summary, we report that malignant T cells produce IL‐4, a type 2 cytokine (Th2 cell response) that acts as a growth factor and which may play a critical role in PTCL disease mechanism.

Functional Properties of Neoplastic T Cells in Helper T Cell Prolymphocytic Leukaemia with IgM Hypergammaglobulinaemia

A case of T cell prolymphocytic leukaemia of helper/inducer T cell phenotype with IgM hypergammaglobulinaemia in a 65‐year‐old Saudi man is presented. The neoplastic T cells in the patient had an OKT3+, OKT4+, OKT8−, OKT11+, OKCLL+, OKIa1+, OKDR+, Tac+ phenotype. The presence of OKIa1+, OKDR+, and Tac+ antigens indicates that the leukaemic T cells were in an activated state. The cells responded to phytohaemagglutinin, but showed a diminished response to concanavalin A. The reduced interleukin 2 receptor expression and interleukin 2 production were associated with defective concanavalin A‐induced proliferation. There was suppression of mixed lymphocyte culture reaction between the patient and two healthy donors in response to concanavalin A. In vitro immunoglobulin production experiments demonstrate that the leukaemic T cells provided an enhanced helper cell function to produce IgM, and suppressor cell function to produce IgG immunoglobulins by pokeweed mitogen‐induced normal B lymphocyte differentiation. In this study we also found that the patients T cells proliferate in response to lipopolysaccharides, thus providing the first evidence that leukaemic (OKT4+) T cells from a prolymphocytic leukaemia patient can be stimulated by lipopolysaccharides.