Relationship between T lymphocyte responsiveness and T-helper1/T-helper2 type cytokine release in chronic hepatitis C: a critical reappraisal.

Recruitment of virus-specific T lymphocyte subpopulations to liver sites in chronic hepatitis C virus (HCV) infection implies a key role for the immune response in host-virus interaction. In spite of a multispecific and polyclonal cytotoxic function exerted by CD8+ lymphocytes, CD4-mediated activity is weak. This allows the infection to persist which in turn is responsible for the development of chronic hepatitis C (CH-C). Such a finding outlines the occurrence of a possible relationship between cytokine (CK) production by CD4 subsets, i.e. T helper (Th)1 or Th2 cells, and the clinical outcome. A prevalence of Th1-derived CK occurs in infected liver, while increased amounts of Th2-related CK are usually found in peripheral blood. Moreover, peripheral blood mononuclear cell (PBMC) cultures from CH-C subjects exhibit an impaired interferon (IFN)-gamma production and an increase of interleukin (IL)-12 p70 release after stimulation. The latter pattern seems to be due to the enhanced release of IL-12 p40 homodimers, which antagonize IL-12 p70 bioactivity and favour IL-10-induced effects. These results suggest that further extensive studies on the imbalance of the CK network at a molecular level are required to improve the therapeutical approach in CH-C subjects.

[Autoantibodies in chronic hepatitis C. Markers of autoimmunity or non-specific events?]. / Autoanticorpi nell'epatite cronica da virus C. Marcatori di autoimmunità o eventi aspecifici?

In the light of the high prevalence of non organ-specific autoantibodies in chronic hepatitis C, the possibility that such a finding may represent the consequence of a viral, autoimmune or overlapping disease should be considered, which may in turn require a different therapeutical approach. It is known, anyway, that the diagnosis of autoimmune hepatitis is based on a set of epidemiological, clinical, biochemical, histological criteria and autoantibody pattern. In 113 cases of chronic hepatitis with HCV infection, we determined the presence of non organ-specific autoantibodies [anti-nuclear (ANA), anti-smooth muscle (SMA), anti-liver-kidney microsomal antibodies (LKM), anti-mithocondrial antibodies (AMA)] and described the epidemiological, clinical, biochemical, histological characteristics and therapeutic response to interferon. 40 patients (35%) exhibited non organ-specific autoantibodies: 25 patients were SMA positive (Vasal pattern), 4 ANA positive (Speckled pattern), 7 ANA (Speckled pattern) + SMA (Vasal pattern) positive and 4 LKM positive. All subjects with HCV infection and autoantibodies did not display additional criterias of autoimmunity, including the same outcome to interferon therapy when compared to HCV positive patients without autoantibodies. The failure to determine clinical features, associated to autoimmunity in HCV positive patients with autoantibodies, suggests that autoantibody occurrence may represent a fortuitous event during the course of HCV infection.

[Acute disseminated encephalomyelitis as initial clinical manifestation of common variable immunodeficiency. A case report]. / Encefalomielite acuta disseminata come manifestazione clinica iniziale nel deficit immunologico comune variabile. Descrizione di un caso.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by severe and recurrent infections which affect both lung and gastrointestinal systems. On the contrary, central nervous system involvement, related to virus infections, is an important, rare and usually fatal complication occurring in a later phase of the disease. Furthermore, CVID may predispose to a variety of autoimmune diseases. Here, we report the case of a 20 years old girl who developed acute disseminated encephalomyelitis as the first clinical feature in CVID. The infective agent was not determined and there was no history of recent vaccinations. CVID was diagnosed on the basis of the significant reduction of serum immunoglobulin concentration, in the absence of either diseases responsible for secondary immunodeficiency or functional and/or quantitative abnormalities of lymphocyte subsets, phagocytes and complement fractions. The treatment with high doses of native intravenous immunoglobulins (IVIG) combined with corticosteroids in the early phase led to a complete recovery with restitutio ad integrum. This case outlines the possible relationship between autoimmune diseases and infections in CVID, as suggested by the finding of either viral encephalitis in CVID patients and the well-known autoimmune pathogenesis of acute disseminated encephalomyelitis. In such a condition, the combination of IVIG and corticosteroids may offer considerable advantages in terms of therapeutical efficacy.

[Pericardial involvement as initial manifestation of multiple myeloma]. / Interessamento pericardico come manifestazione iniziale di mieloma multiplo.

Pericardial involvement is a rare complication of multiple myeloma, caused by amyloidosis, infections, or plasmacell infiltration, usually at late or terminal disease stage. We report a patient with pericarditis coming from a department of Cardiology where a preceding (15 years before) diagnosis of breast cancer and present bloody pericardial effusion with probably malignant cells permitted at first to orientate towards metastatic pericardial involvement in breast cancer. Laboratory findings (pancytopenia, hypogammaglobulinemia, proteinuria) suggested to perform bone marrow aspirate, serum and concentrated urine immunoelectrophoresis, measurement of 24-h urine protein excretion, and further cytologic and immunocytochemical assay of pericardial fluid. Acquired data allowed to diagnose light chain multiple myeloma with pericardial involvement caused by plasmacell infiltration. We diagnosed this complication, representing first and main clinical feature of multiple myeloma, owing to a complete clinical and laboratory evaluation and repetition of cytologic and immunocytochemical assay of pericardial fluid.