High-dose immunosuppression with autologous stem cell transplantation in severe refractory systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an immune-mediated disease that is responsive to suppression or modulation of the immune system. Patients with SLE who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide (Cy), represent a subset of patients at high risk of early death. We investigated the efficacy and toxicity of high-dose immunosuppression and autologous hematopoietic stem cell transplantation (SCT) to treat such patients. Six patients (all female, age 15-29 years) with severe refractory SLE were enrolled in the clinic of our institution from 1998 to 2003. All patients were seriously ill, with SLE disease activity indices (SLEDAI) of 6-30, including two cases with central nervous system lupus, one case with lung vasculitis, and three cases with nephritis and nephrotic syndrome. All patients were registered in the European Group for Blood and Marrow Transplantation (EBMT)/European League Against Rheumatism (EULAR) database. Previous immunosuppression included pulse Cy intravenous, prednisolone (standard doses and pulse therapy), oral Cy and azathioprine, with little or no effect on disease progression. Autologous hemopoietic stem cells were collected from bone marrow (n = 4) or mobilized from peripheral blood with Cy and granulocyte colony-stimulating factor (G-CSF) (n = 2). Pre-transplant conditioning regimens included BEAM +/- ATG (n = 2), melphalan 140 mg/m2 + etoposid 1600 mg/m2 (n = 2) and Cy 200 mg/kg +/- ATG (n = 2). Median time to an absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L and platelet count greater than 50 x 10(9)/L was 13 and 15 days, respectively. Three patients died on days 11, 22 and 63 due to transplant-related complications. The follow-up is now 60 and six months for two patients (complete remission), and 42 months for one other patient (partial response). All patients had experienced multiple and severe episodes of infections pre-SCT and long-term history of corticosteroid therapy (3-14 years). We conclude that achievement of prolonged, corticosteroid-free remissions is a reality. Judicious selection of patients earlier in disease or in remission, but with a high risk of relapse or further progression, will diminish transplantation-related mortality.

[Association between DNA antibodies levels in the blood of patients with multiple sclerosis and clinical presentation of the disease]. / Urovni antitel k DNK v krovi bol'nykh rasseiannym sklerozom v zavisimosti ot klinicheskikh kharakteristik zabolevaniia.

Multiple sclerosis (MS) as an autoimmune disease is characterized by occurrence of high titres of antibodies (AB) to cell structures and autoantigens. Various AB-mediated effector mechanisms can participate directly in the pathogenesis of demyelinisation damaging myelin, oligodendrocytes and nervous fibres. Antinuclear AB, including anti-DNA AB are an example of activation of humoral immunity in MS. Pathogenetic and clinical value of these AB is investigated insufficiently. The aim of this study was estimation of the AB titers in MS patients from two populations of Russia in relation to clinical features of MS. Results of examination of 83 patients with definite MS from Novosibirsk and Moscow (49 and 34 patients) are analyzed. Groups of comparison consisted of healthy donors and patients with SLE of the same age. Use of identical methods in the analysis of the data received in two various populations made the data objective as much as possible and revealed the strongest clinico-biochemical associations. Levels of AB to both native and denaturated DNA were studied. Comparison of several test-systems showed that the system produced by "Specialized scientific Labs" Company has the best sensitivity. In two populations of MS patients the levels of AB in plasma were similar and associated between each other, higher than in donors, but lower than in SLE patients. In both groups MS patients with secondary progressive MS had higher percent of samples of plasma with average and high levels of AB. In the Novosibirsk group associations of levels of AB with parameters of disease severety (EDSS and a number of FS scales) were seen. In the Moscow group levels of AB to DNA were significantly associated with time from the disease onset to certain level of disability (EDSS 3); both the analysis of average values and the correlation analysis showed a weak association of AB to DNA level and MS duration. The data testify that AB to DNA play a more important role in MS pathogenesis than was considered earlier. Catalytic AB as a part of anti-DNA AB may play a special role.

[Association of TAP1/TAP2 gene polymorphism with inflammatory urogenital diseases combined with joint diseases]. / Assotsiirovannost' polimorfizma genov TAP1/TAP2 s vospalitel'nymi zabolevaniiami urogenital'nogo trakta, sochetaiushchimisia s porazheniiami sustavov.

AIM: To study association of TAP1/TAP2 gene polymorphism with urogenital infections combined with joint lesions. MATERIALS AND METHODS: Of 139 patients examined 45 ones had inflammation caused by Chlamydia trachomatis (17 had joint disease), 42 had Mycoplasma hominis infection (joint lesions in 17 cases). Method of amplification was used on the basis of specific primers (ARMS). RESULTS: Patients infected with C. trachomatis significantly more frequently had allele TAP1-02011 and TAP2-0201 (RR = 18.5, p < 0.01 and RR = 4.61, p < 0.05, respectively). Joint lesion in patients with chlamydial infection was associated with allele TAP1-02011 (RR = 11.92, p < 0.05). In mycoplasmosis association with joint lesions there is a significant link of joint syndrome with heterogeneous combination threonine/alanine in gene TAP2 position 565 (RR = 4.22, p < 0.05). CONCLUSION: The findings can be used for predicting the joint syndrome development in patients with urogenital infection.