Use of anti-tumor necrosis factor alpha therapy in patients with concurrent rheumatoid arthritis and hepatitis B or hepatitis C: a retrospective analysis of 32 patients.

The safety of tumor necrosis factor-alpha (TNF-α) inhibitors in the setting of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is controversial. The use of anti-TNF-α in rheumatoid arthritis (RA) is associated with an increased risk of hepatitis re-activation. This paper reports experience of using etanercept and adalimumab in 32 patients with RA and previous HBV or HCV infection. No cases of HBV or HCV reactivation were seen. In just over a fifth of patients, increased transaminases levels were seen, which were associated with concomitant use of disease-modifying antirheumatic drugs, isoniazid prophylaxis, or alcohol abuse. In our experience, anti-TNF-α therapy appears to be safe in RA patients with previous HBV or HCV infection, but monitoring remains necessary in these patients.

Complement and autoimmunity.

The complement system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens through direct killing or stimulation of phagocytosis. However, in recent years, the immunoregulatory functions of the complement system were demonstrated and it was determined that the complement proteins play an important role in modulating adaptive immunity and in bridging innate and adaptive responses. When the delicate mechanisms that regulate this sophisticated enzymatic system are unbalanced, the complement system may cause damage, mediating tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical manifestations of several autoimmune diseases, such as systemic lupus erythematosus, vasculitides, Sjögren's syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis. Complement deficiencies have been associated with an increased risk to develop autoimmune disorders. Because of its functions, the complement system is an attractive therapeutic target for a wide range of diseases. Up to date, several compounds interfering with the complement cascade have been studied in experimental models for autoimmune diseases. The main therapeutic strategies are inhibition of complement activation components, inhibition of complement receptors, and inhibition of membrane attack complex. At present, none of the available agents was proven to be both safe and effective for treatment of autoimmune diseases in humans. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system could constitute a viable strategy for the treatment of autoimmune conditions in the decades to come.

Role of the complement system in rheumatoid arthritis and psoriatic arthritis: relationship with anti-TNF inhibitors.

The complement system is an essential component of innate immunity and also plays an important role in modulating adaptive immunity. It comprises more than 30 plasma and membrane-bound proteins and can be activated through three pathways: the classical, the alternative and the lectin pathways. Its activation contributes to the pathogenesis of several autoimmune and inflammatory conditions. The evidence of complement activation in synovial fluid of Rheumatoid Arthritis (RA) patients is abundant, while few data exist in Psoriatic Arthritis (PsA) patients. Levels of complement proteins are generally depressed in the synovial fluid of patients with RA, reflecting consumption of complement. On the other hand, elevated levels of several complement cleavage products have been observed in synovial fluid. Involvement of complement in the pathogenesis of RA was also confirmed in animal models of arthritis: mice deficient for complement proteins are protected against the development of collagen-induced arthritis and administration of the anti-C5 monoclonal antibody prevents the onset of this arthritis. In the last decade anti-tumor necrosis factor agents have shown to be effective for the treatment of both RA and PsA and some studies suggest that the interaction between TNFα and complement system may contribute to the pathogenesis of these diseases. Reduction of the complement activation could be one of the mechanism by which TNFα-inhibitors exert their effectiveness in inflammatory arthritides. Because of these findings, complement could be an attractive therapeutic target both in RA and in PsA.

High levels of peripheral blood NK cells in women suffering from recurrent spontaneous abortion are reverted from high-dose intravenous immunoglobulins.

PROBLEM: To determine the levels of peripheral blood natural killer (NK) cells in healthy women and recurrent aborters, and the effect of intravenous immunoglobulins (IVIGs) on these levels. METHOD OF STUDY: A total of 659 women were evaluated for NK cells by means of flow cytofluorimetry: 42 non-pregnant healthy women, 394 non-pregnant recurrent spontaneous abortion (RSA) women, 36 pregnant healthy women and 187 pregnant RSA women. Fifty-four of the pregnant RSA women were treated with IVIG; in 18 of them NK cells were measured immediately before and after the very first IVIG infusion (0.5 g/kg body weight). RESULTS: Blood NK cell results were increased in RSA pregnant/non-pregnant women, and significantly reduced by IVIG, even after the very first infusion. In RSA pregnant women treated by means of IVIG therapy, 92.3% success rate was observed. CONCLUSIONS: High levels of NK cells are detected in women affected by RSA. IVIGs are capable of decreasing them with a short- and long-term efficacy, allowing having a very high success rate of pregnancies in RSA women.