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Using two independent PCR-based quantification techniques, we have determined the levels of IL1 beta, IL2, IL4, IL6, IL10, IFN gamma and TNF alpha mRNA in multiple sclerosis patients at the moment of diagnosis of the disease and prior to any immunosuppressive treatment. These patients exhibit markedly reduced IL2 and IL10 mRNA expression accompanied by decreased levels of TNF alpha mRNA. Our results add to the evidence that IL10 plays a role in multiple sclerosis and suggest that decreased production of this interleukin allows the proliferation of autoreactive T cells at the onset of the disease.

Purpose: To establish a human leukocyte antigen (HLA) association in a homogeneous population of patients with pars planitis., Methods: A strict set of inclusion parameters was established for the diagnosis of pars planitis. Forty patients with pars planitis who met these criteria underwent HLA analysis of class I and II phenotypes., Results: HLA-B8 was present in 15 (37.5%) of 40 patients versus 85 (19.7%) of 431 controls (relative risk, 2.44; P = 0.011). HLA-B51 was present in 9 (22.5%) of 40 patients versus 51 (11.8%) of 431 controls (relative risk, 2.16; P = 0.049). HLA-DR2 was present in 27 (67.5%) of 40 patients versus 121 (28.0%) of 431 controls (relative risk, 5.32; P < 0.0001). HLA-DR2 has been associated with multiple sclerosis (MS). Exclusion of five patients with pars planitis in whom MS subsequently developed did not change the significance of these findings., Conclusions: The strongest association of pars planitis with HLA-DR2 and the temporal development of MS in some patients with pars planitis further supports an association between pars planitis and MS.

Fifty-four patients with clinically definite multiple sclerosis were typed for HLA-A, B, C, DR and DQ antigens. HLA-DQ was not a better disease marker than the previously described HLA-DR and B markers. The patients were subdivided according to the clinical evolution of their disease, age at onset and sex. HLA-DR2 was significantly associated with females having a relapsing-remitting course of the disease and HLA-B8 and B35 were significantly associated with males having a chronic-progressive course of the disease. A role is postulated for defects in the sex hormone balance in females and for microbial infections in males as dominant environmental triggers in the development of autoreactivity.

Interferon (IFN) production by peripheral blood mononuclear cells after induction with one purified and three crude viral antigens was studied in 29 patients with stable multiple sclerosis (MS) and 29 healthy controls. Antiviral substance produced was characterized as interferon-alpha. MS patients produced significantly less IFN-alpha after induction with mumps and purified measles virus antigens and the same tendency was seen after induction with rubella virus antigen. However, when herpes simplex virus antigen was used as the stimulating agent, no difference was seen between MS patients and controls. The decreased ability to produce IFN-alpha was associated with the histocompatibility antigen Dw2. Control subjects positive for Dw2 also produced less IFN-alpha than Dw2-negative controls. In conclusion, we suggest that the observed impaired interferon-alpha production in MS is at least partially due to a high prevalence of Dw2 antigen in this disease.

We compared healthy blood donors with and without HLA-Dw2 and -Dw3 in immunity assays, the results of which have been found to be abnormal in multiple sclerosis or autoimmune diseases. Tests included lymphocyte blast transformation responses to rubella, mumps and purified tuberculin (PPD), in vitro production of IgG and interferons, natural killer (NK) cell function and measurement of serum antibodies to measles, rubella, mumps and herpes simplex viruses. HLA-Dw2-positive subjects had a lower lymphocyte blast transformation response to rubella virus antigen and a lower NK cell function compared with HLA-Dw2-negative subjects. The presence of HLA-Dw3 was associated with an increased spontaneous and mumps virus-induced immunoglobulin production. No significant differences were found in other assays. These results support the existence of HLA-Dw2- and Dw3-associated deviation of immune responsiveness, which may contribute to the susceptibility of multiple sclerosis or other autoimmune type diseases.

By means of two different IgM-capture assays, enterovirus-specific IgM responses were shown in 9 of 14 (64%) patients with chronic relapsing pericarditis. This finding suggests persistent enterovirus infection, particularly coxsackie B virus infection. IgM responses persisted for at least 1 year and for up to 10 years after onset of symptoms. In contrast, patients with acute enterovirus infections, including acute pericarditis, had transient responses. Among patients with acute pericarditis, the level of IgM antibody was significantly higher in those who subsequently relapsed (mean 1.21, range 0.6-2.0 optical density [OD] units) than in those who did not (0.4, 0.2-0.9 OD units; p less than 0.01). Of 86 patients with dilated cardiomyopathy, 28 (33%) showed enterovirus-specific IgM responses which were present for up to 19 months before transplantation and persisted up to 4 years afterwards. Although the distribution of HLA types in these patients was similar to that in the general population, the frequency of the HLA A2 haplotype was significantly higher in those who were IgM positive. IgM antibody was significantly more common in those who had had symptoms for longer than a year before transplantation than in those with a shorter duration of symptoms (1 of 21 vs 8 of 23; p less than 0.02). Persistent virus-specific serum IgA responses were also shown in patients with chronic cardiac disease.