Biomedical applications of snake venom: from basic science to autoimmunity and rheumatology.

Snake venoms have components with diverse biological actions that are extensively studied to identify elements that may be useful in biomedical sciences. In the field of autoimmunity and rheumatology, various findings useful for the study of diseases and potential drug development have been reported. The study of disintegrins, proteins that block the action of integrins, has been useful for the development of antiplatelet agents and principles for the development of immunosuppressants and antineoplastics. Several proteins in snake venoms act on the coagulation cascade, activating factors that have allowed the development of tests for the study of coagulation, including Russell's viper venom time, which is useful in the diagnosis of antiphospholipid syndrome. Neurotoxins with either pre- or postsynaptic effects have been used to study neurogenic synapses and neuromuscular plaques and the development of analgesics, muscle relaxants and drugs for neurodegenerative diseases. Various components act by inhibiting cells and proteins of the immune system, which will allow the development of anti-inflammatory and immunosuppressive drugs. This review summarizes the usefulness of the components of snake venoms in the fields of autoimmunity and rheumatology, which can serve as a basis for diverse translational research.

A giant fibrinoid pericardial mass in a patient with rheumatoid arthritis: a case report.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints, which may extend to extra-articular organs. Extra-articular manifestations have been considered as prognostic features in RA, and pericardial disease is one of the most frequent occurrences. Rheumatoid arthritis pericarditis is usually asymptomatic and is frequently found on echocardiography as pericardial thickening with or without mild effusion. Severe and symptomatic cases are rare, but pericardial masses are even rarer. We report a patient with erosive, nodular seropositive RA, and progressive functional deterioration owing to a giant pericardial mass compressing the right cardiac chambers. CASE SUMMARY: The patient was a 79-year-old man. Cardiac magnetic resonance imaging revealed a pericardial lesion measuring 10 × 9 × 6 cm with complex structures in its interior, which had compressive effects on the right atrium and right ventricle, severely limiting diastole. Late gadolinium enhancement of the lesion walls and pericardium suggested pericarditis. Surgical resection was performed, and a soft mass with liquid content was extracted. The patient recovered well with improvements in symptoms and the functional status. Histopathological studies ruled out neoplasm, vasculitis, and infection, and the entire mass showed fibrinoid material associated with fibrinoid pericarditis. DISCUSSION: Symptomatic RA pericarditis is a rare cardiac manifestation of RA, whilst associated significant haemodynamic compromise is even rarer. The condition could manifest with a giant compressive pericardial mass composed of fibrinous material, with particular involvement of the right ventricle. Exclusion of other conditions, such as neoplasms and infections, is necessary.

Anti-alpha-actinin antibodies are part of the anti-cell membrane antibody spectrum that characterize patients with lupus nephritis.

Anti-membrane autoantibodies (MbA) have been reported in sera from patients with lupus nephritis (LN) but the targets of the MbA remain to be explored, which is the aim of the current study. Sera were collected from 40 patients with LN determined by renal biopsy, and from 30 systemic lupus erythematosus (SLE) patients without clinical evidence of LN. Thirty autoimmune disease control patients (rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis), and 30 healthy controls were also included. Using flow cytometry, the presence of anti-MbA was explored revealing that IgG anti-MbA positivity was associated with LN (62.5% vs 13.3%) when compared to non-LN SLE patients, autoimmune disease patients (6.7%) and healthy controls (0%). Next, using purified plasma membrane fractions from human embryonic kidney (HEK) cells, the more prominent targets and their occurrence rates were located at 50 kDa, 60/65 kDa, 90 kDa, 110 kDa, 180 kDa and 220 kDa. Alpha-actinin (110 kDa) autoAb was characterized as a major target in LN patients positive for anti-MbA, and anti-MbA binding activity was reduced (36.9 ± 13.7%) in the presence of α-actinin. Laminin (200 kDa) was also characterized as a minor target, which was not the case for annexin A2 (36 kDa). Finally, anti-MbA IgG subclass analysis indicated a predominance of IgG2. In conclusion, IgG anti-MbA were detected at high levels in LN patients supporting a primary pathogenic role for anti-MbA and anti-MbA/α-actinin+ in LN that needs further research.

Annexin A2 autoantibodies in thrombosis and autoimmune diseases.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by arterial, venous or small-vessel thrombotic events, and recurrent miscarriages or fetal loss. APS diagnosis is based on the repeated detection of anti-phospholipid (PL) antibodies (Ab), typically associated with anti-ß2 glycoprotein I (ß2GPI)-Ab. Recent studies suggest that anti-ß2GPI Ab activity involves a protein complex including ß2GPI and annexin A2 (ANXA2). Anti-ANXA2 Ab recognizes this complex, and these Ab can effectively promote thrombosis by inhibiting plasmin generation, and by activating endothelial cells. Therefore, anti-ANXA2 Ab represent a new biomarker, which can be detected in up to 25% of APS patients. Moreover, anti-ANXA2 Ab have been detected, in thrombotic associated diseases including pre-eclampsia, in other autoimmune diseases, and in cancer.

Efficacy and safety of anti-interleukin 6 receptor monoclonal antibody (tocilizumab) in Colombian patients with Takayasu arteritis.

PURPOSE: The aim of this study was to describe the efficacy and safety of anti-interleukin 6 receptor antibody (tocilizumab [TCZ]) in patients with severe or refractory Takayasu arteritis (TA). METHODS: We describe 8 Colombian patients with severe and/or refractory TA treated with TCZ during a period of at least 9 months. Clinical, radiological, biological, and associated treatments were evaluated before, during, and after TCZ infusions. RESULTS: The median age at evaluation was 31 years (12-43 years). All patients were female and experienced clinical and biological improvement, in addition to a corticosteroid-sparing effect from a median dose of 50 mg/d at baseline (30-60 mg/d) to 6.25 mg/d (2.5-10 mg/d) at 9 months. In 4 cases, in which imaging studies were available, an improvement was observed. The median duration of TCZ infusions was 18 months (9-36 months). Major adverse effects related to TCZ were not evidenced during a period of at least 9 months of treatment. One relapse was observed. Tocilizumab was continued in all cases until the last follow-up. CONCLUSIONS: This study shows a clinical, biological, and radiological response in patients with refractory TA treated with TCZ.