Alaa Ahmed

A study of 20 SLE patients with intravenous immunoglobulin--clinical and serologic response.

Objective: To test the clinical response of systemic lupus erythematosus (SLE) patients to intravenous immunoglobulins (IVIg), and whether the clinical response of IVIg treatment in SLE is accompanied by modification of SLE-associated autoantibodies/antibodies (Abs) and complement levels. Methods: Twenty SLE patients were treated with high-dose (2 g/kg) IVIg monthly, in a 5-d schedule. Each patient received between 1-8 treatment courses. They were evaluated for the clinical response, Systemic Lupus Activity Measure (SLAM) score before and after IVIg, levels of antinuclear antibody (ANA), dsDNA (double-stranded DNA), SS-A or SS-B, ENA (extractable nuclear antigens), C3 and C4 levels before and after the treatment, and before and after each treatment course. Results: A beneficial clinical response following IVIg treatment was noted in 17 out of 20 patients (85%). Few clinical manifestations responded more to treatment: arthritis, fever, thrombocytopenia, and neuropsychiatric lupus. In 9 patients evaluated before and after IVIg, mean SLAM score decreased from 19.3 ± 4.7 to 4 ± 2.9 (P < 0.0001). There was a tendency towards abnormal levels of complement and Abs before IVIg courses among the treatment responders compared with the non-responders, and similarly the former tended to have normalization of their abnormal levels more than the latter. These differences were found statistically significant only with respect to C4 and SS-A or SS-B levels before IVIg courses. Conclusion: IVIg has a high response rate among SLE patients. A combination of clinical manifestations, Abs and complement levels may aid in the future in predicting who among SLE patients will benefit more from IVIg treatment.

Detection of retroviral antibodies in primary biliary cirrhosis and other idiopathic biliary disorders

Summary Background Retroviruses have been implicated in the aetiology of various autoimmune diseases. We used immunoblots as a surrogate test to find out whether retroviruses play a part in the development of primary biliary cirrhosis. Methods We did western blot tests for HIV-1 and the human intracisternal A-type particle (HIAP), on serum samples from 77 patients with primary biliary cirrhosis, 126 patients with chronic liver disease, 48 patients with systemic lupus erythematosus, and 25 healthy volunteers. Findings HIV-1 p24 gag seroreactivity was found in 27 (35%) of 77 patients with primary biliary cirrhosis, 14 (29%) of 48 patients with systemic lupus erythematosus, 14 (50%) of 28 patients with chronic viral hepatitis, and nine (39%) of 23 patients with either primary sclerosing cholangitis or biliary atresia, compared with only one (4%) of 24 patients with alcohol-related liver disease or α 1 -antitrypsin-deficiency liver disease, and only one (4%) of 25 healthy volunteers (p=0·003). Western blot reactivity to more than two HIAP proteins was found in 37 (51%) of patients with primary biliary cirrhosis, in 28 (58%) of patients with systemic lupus erythematosus, in 15 (20%) of patients with chronic viral hepatitis, and in four (17%) of those with other biliary diseases. None of the 23 patients with either alcohol-related liver disease or α 1 -antitrypsin deficiency, and only one of the healthy controls showed the same reactivity to HIAP proteins (p Interpretation The HIV-1 and HIAP antibody reactivity found in patients with primary biliary cirrhosis and other biliary disorders may be attributable either to an autoimmune response to antigenically related cellular proteins or to an immune response to uncharacterised viral proteins that share antigenic determinants with these retroviruses.

Serum autoantibodies in patients with primary sclerosing cholangitis

BACKGROUND/AIM Primary sclerosing cholangitis is a chronic cholestatic syndrome with a presumed autoimmune basis frequently associated with inflammatory bowel disease. The aim of this study was to determine the profile and significance of serum autoantibodies in patients with primary sclerosing cholangitis. METHODS Serum samples taken from 73 untreated patients (32 female and 41 male, median age 45 years) with well-defined primary sclerosing cholangitis, and from 75 healthy age- and sex-matched controls were assayed for 20 different autoantibodies. RESULTS Of 73 patients, 71 (97%) were positive for at least 1 autoantibody; whereas 59/73 patients (81%) were positive for > or =3 antibodies. Patients with primary sclerosing cholangitis had a significantly greater rate of positivity than controls for antinuclear, anticardiolipin, antineutrophil cytoplasmic, and antithyroperoxidase antibodies as well as rheumatoid factor. The rate of positivity and serum levels of any of these 20 autoantibodies were not significantly different between patients with primary sclerosing cholangitis and inflammatory bowel disease and those without inflammatory bowel disease. Anticardiolipins were the single group of antibodies that had a significant correlation with the Mayo risk score (r=0.49, p<0.001) and histologic stage of disease (r=0.30, p<0.01). CONCLUSIONS Primary sclerosing cholangitis is associated with a high proportion of non-organ specific autoantibodies. Anticardiolipin antibodies appear to be related to the severity of primary sclerosing cholangitis and may be a useful prognostic marker.

Serologic and Clinical Response to Treatment of Systemic Vasculitis and Associated Autoimmune Disease with Intravenous Immunoglobulin

Background: Autoimmune vasculitides cannot always be controlled by steroids and immunosuppressive drugs. Intravenous immunoglobulin (IVIg) treatment was found beneficial in several vasculitides including systemic and organ–specific diseases. In this article we tested whether the beneficial clinical response of IVIg treatment in vasculitides was accompanied by a decrease in vasculitis–associated autoantibody levels. Methods: Ten patients diagnosed as having vasculitis were treated with high–dose (2 g/kg) IVIg monthly, in a 5–day schedule. In all the patients, other therapeutic measures failed to control disease progression prior to IVIg treatment. Each patient received between 1 and 6 treatment courses. All patients were evaluated for the levels of 5 autoantibodies (Abs) related to vasculitis before and after each treatment course. Results: In 6 out of the 10 patients, a beneficial clinical response followed IVIg treatment. Moreover, no treatment–related adverse effects were observed in any of the patients. Anti–myeloperoxidase antibodies and cytoplasmic–antineutrophil cytoplasmic antibodies levels decreased concomitantly with the clinical improvement observed in the patients with Churg–Strauss vasculitis and Wegener’s granulomatosis, respectively. Levels of cytoplasmic–antineutrophil cytoplasmic antibodies (ANCA) with specificity for bacteridial/permeability–increasing protein and human lysosomal–associated membrane protein increased after each treatment course, but returned to normal values before the following one. Conclusions: When other therapeutic measures, such as immunosuppressive therapy, fails to control disease manifestations in patients with vasculitides, IVIg is a possible effective intervention method with a high response rate. IVIg probably exerted its effects on disease progression via different mechanisms. Among these mechanisms, a decrease in relevant Ab levels is often found (probably by anti–idiotypes in IVIg), and thus ANCA levels are expected to associate with disease activity.

Autoantibody Level Modification in Adult Patients with Idiopathic Thrombocytopenic Purpura following Intravenous Immunoglobulin Treatment

The aim of this study was to determine whether treatment of patients with immune thrombocytopenic purpura (ITP) with intravenous immunoglobulin (IVIg) is associated with a modification in the antiplatelet glycoprotein (GP) antibodies (Abs). Fourteen patients with ITP (11 females and 3 males, mean age 36.6 years, range 18–72) received one to four IVIg treatment courses. The preparation used was ISIVEN that was given in a dose of 2 g/kg body weight in a 5-day schedule and in monthly intervals. Levels of IgG, IgM and IgA isotypes of Abs to GPs IIb/IIIa and Ib/IX were measured before the treatment, and before and after each treatment course. Two patients did not respond to IVIg, 6 had a temporary response, 5 had a sustained response and 1 patient responded well to the treatment but was lost to follow-up. The patients had a high prevalence of serum Abs directed against GPs IIb/IIIa and Ib/IX before the treatment, and the mean IgG isotype levels of both Abs increased after each treatment course, and decreased again before the following course began. Whenever high Ab levels of either isotype (>10 U/ml) were detected before the treatment, they were significantly decreased before the last treatment course. The elevated levels of IgG Abs to IIb/IIIa and Ib/IX after every course are probably a result of displacement of these Abs from Fc receptors by the IVIg, rather than of exogenous infusion of these Abs contained within the IVIg, whereas the decrease in high Ab levels after a few treatment courses results from the immunomodulatory effects of IVIg: suppression of Ab formation, and the presence of anti-idiotypes.

Detection of Antibodies to Gangliosides and Glycolipids in Various Intravenous Immunoglobulin (IVIg) Preparations

The aim of this study was to examine the presence of antibodies to GM1 and sulfatide in various IVIg preparations. Five brands of commercially available human IVIg (Sandoglobulin, Isiven, Cytogam, Omrigam and Cutter) were examined and compared. Serial dilutions of each of the above preparations were prepared at a working range of 0.009 to 25.0 mg/ml IVIg, and screened by a standard 96-well microplate EIA for autoantibodies to the ganglioside GM1 and to the glycolipid sulfatide. The various IVIg preparations (Omrigam, Cytogam, Sandoglobulin, Isiven), except for Cutter IVIg, contained low to medium titers of the autoantibodies tested. Omrigam and Cytogam IVIg contained low titer of antibodies to GM1, and medium-titer of antibodies to sulfatide, whereas Sandoglobulin and Isiven contained only low-titer of autoantibodies to sulfatide. The presence of natural autoantibodies to myelin in human sera may explain the presence of the tested antibodies within IVIg preparations. Measurements of antibodies to ganglioside and glycolipid in sera of Guillain-Barré patients immediately following IVIg, would probably not reveal antibody decrease. Alternatively, long-term (several weeks) follow-up of titers might result in their modification due to inhibition of antibodies production by IVIg.

Autoimmune Thrombocytopenia Purpura

Autoimmune thrombocytopenia purpura (AITP) is a common haematological disorder caused by antiplatelet autoantibodies that lead to increased clearance of platelets by the reticuloendothelial system. Patients with AITP have low platelet counts and a bleeding tendency affecting the skin and mucosa. AITP can be classified into 2 main clinical syndromes: (a) idiopathic (primary or essential) thrombocytopenia (ITP) and (b) secondary AITP. Secondary AITP occurs in conjunction with a primary (usually autoimmune or malignant) disorder, and accounts for the majority of cases of AITP. ITP has an unknown aetiology, and diagnosis is made by exclusion of secondary AITP. Laboratory diagnosis of AITP relies on detection of platelet-associated immunoglobulin or on the demonstration of platelet autoantibodies that react with specific target antigens on the platelet surface. Treatment of AITP involves therapy with corticosteroids, followed if necessary by splenectomy. The use of high-dosage intravenous immunoglobulin G may improve the response to corticosteroids.