Martin Panelius

HLA class II associated risk and protection against multiple sclerosis—a Finnish family study

We analyzed the HLA class II haplotypes in 249 Finnish nuclear families and compared the frequencies of parental haplotypes transmitted or non-transmitted to multiple sclerosis (MS) patients. The most important predisposing haplotype was DRB1*15-DQB1*0602 (P<10(-6)) as expected and a weak predisposing effect of DRB1*04-DQB1*0302 was revealed after the elimination of DRB1*15-DQB1*0602. HLA-DRB1*01-DQB1*0501 and DRB1*13-DQB1*0603 were negatively associated with MS in transmission disequilibrium test, but only the DRB1*13-DQB1*0603 association remained significant (P=0.008) after the elimination of DRB1*15-DQB1*0602 haplotypes. Based on this study HLA class II haplotypes exhibit both predisposing and protective effects in MS.

Measles Virus Antibody in Cerebrospinal Fluids from Patients with Multiple Sclerosis

A strong measles-specific gel precipitation reaction was found in the cerebrospinal fluid (C.S.F.) of two patients with multiple sclerosis (M.S.) (total of 15 tested). The serum and C.S.F. specimens from these two patients were tested for measles antibody by six assay methods. The results were compared with those obtained from serum and C.S.F. specimens of a patient with subacute sclerosing panencephalitis (S.S.P.E.). The gel precipitation line produced by the C.S.F. from the M.S. patients was identical with one of the three lines produced by the C.S.F. from the S.S.P.E. patient. The main antigenic component responsible for measles antibody appearing in the C.S.F. of the S.S.P.E. patient and the M.S. patients was also electrophoretically similar, and the corresponding antibody was associated with IgG. The serum/C.S.F. antibody titre ratios with the various assay methods used suggest that the C.S.F. antibodies are mainly to other than envelope components of measles virus. No complement-fixing antibody against 27 other viruses or Mycoplasma pneumoniae was found in the C.S.F. of the two M.S. patients.

Antibodies against different viral antigens in cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases.

Antibodies against structural antigens of measles virus were measured in cerebrospinal fluids (CSF) of multiple sclerosis (MS) patients and controls. The patient group included 63 cases with “probable” and 24 cases with “possible” MS, while the control group consisted of 101 patients with other neurological diseases. Positive rates in MS patients were from 20 to 60 per cent, and in controls from 6 to 9 per cent. Positive rate figures in rubella HI tests were 20 and 2 per cent, respectively. No antibodies against herpes simplex, herpes zoster‐varicella, mumps and RSSE virus were found in complement fixation tests in any of the CSF specimens tested. The presence of measles and rubella antibodies was in positive correlation with higher amounts of IgG and a higher ratio of IgG/albumin. These results suggest that anti‐body production against structural components of measles virus and rubella virus occurs in the central nervous system of some MS patients.

Temporal relationship between environmental influenza A and Epstein-Barr viral infections and high multiple sclerosis relapse occurrence.

Background: Multiple sclerosis (MS) relapses have been associated with viral and bacterial infection epidemics in MS patients who have not used interferon. Objectives: We studied whether environmental viral infections in the general population can be associated with increased MS relapse occurrence using retrospective data from 1986 to 1995 when interferons were not yet available. Methods: Logistic regression modelling was used to compare retrospectively the monthly relapse occurrence from 407 MS patients in Turku University hospital archives and data on ten different specifically diagnosed viral infection epidemics in the general population of Southwestern Finland from 1986 to 1995. The outcome was the odds ratio (OR) of very high relapse occurrence versus low relapse occurrence, or moderate versus low relapse occurrence. Results: After a peak in diagnosed influenza A cases in the general population, the MS relapse occurrence was 6.5 times more likely to be very high (95% CI 1.8–24.0) and 7.1 times more likely to be moderately high (95% CI 1.5–33.2). An increase in MS relapse counts also followed Epstein–Barr virus (EBV) infections (OR 4.4, 95% CI 1.3–15.1), but we found no significant association with adenovirus infections and MS relapses. The MS relapse occurrence was lowest in the summer months July–August (Chi-square test, p < 0.01). Conclusions: Our findings suggest that influenza A and EBV viral infections in the general population are associated with a higher occurrence of exacerbations in MS patients, and thus environmental infection data should be included in epidemiological models on MS relapses.

MEASLES ANTIBODIES DETECTED WITH VARIOUS TECHNIQUES IN SERA OF PATIENTS WITH MULTIPLE SCLEROIS

Hemagglutination inhibition (HI) antibody titers to measles, rubella, mumps, and La Crosse virus in 137 patients with multiple sclerosis and 137 controls matched by date of birth and place of residence were measured and are reported according to age. The measles HI titers were significantly higher in serum specimens of patients with multiple sclerosis (geometric mean 1/82) than in the controls (geometric mean 1/43). In addition, the measles HI titers decreased significantly in the older age groups of the controls, whereas a similar decrease was not observed in the MS patients. No significant differences in the HI titers of rubella, mumps, and La Crosse virus were found between the MS group and the control group. Measles antibodies were further analyzed in a representative smaller series of sera from 49 MS patients and 49 controls by inhibition of salt‐dependent hemagglutinin, gel precipitation, and platelet aggregation. With each of the techniques used, higher levels of measles antibody titers or stronger reactions were observed in the MS group. However, when measles antibodies detected with various techniques were compared in individual serum specimens of MS patients, no clear correlation between the high titers or strong reactions was discernible. The nature of the antibody response to measles virus in MS patients and the light thrown by the results obtained on the etiopathogenesis of multiple sclerosis is discussed.

Measles virus-specific IgM antibodies and IgM-class rheumatoid factor in serum and cerebrospinal fluid of subacute sclerosing panencephalitis patients

Abstract Serum and cerebrospinal fluid (CSF) from 20 subacute sclerosing panencephalitis (SSPE) patients were analyzed with solid-phase radioimmunoassays designed to detect measles virus-specific IgM antibodies and IgM-class rheumatoid factor (RF). Serum and CSF from patients 1 to 16 did not contain measles IgM antibodies or elevated levels of RF. Serum from all and CSF from two of the remaining four patients were apparently measles IgM positive. RF levels were elevated, however, in serum from two and in serum and CSF from another of these four patients. Testing after removal of IgG or RF revealed that patient 17 had both measles IgM and elevated levels of RF in serum, and measles IgM in CSF. Reactivation of measles IgM synthesis was detected in the blood of patient 18. The serum of patient 19 and the serum and CSF of patient 20 contained only elevated levels of RF. The implications of these results are twofold. First, although measles IgM is found in some SSPE patients, it is not found consistently enough to be a marker for the chronic measles virus infection in these patients. Second, the possible interfering presence of RF must be taken carefully into account in any study of IgM antibody persistence.

ASSOCIATION OF MEASLES ANTIBODY ACTIVITY WITH ELECTROPHORETIC FRACTIONS OF CSF IN A PATIENT WITH MULTIPLE SCLEROSIS

The immunoglobulin production in the central nervous system (CNS) of patients with multiple sclerosis (MS) is characterized by an oligoclonal pattern ( L i n k & Miiller 1971). Similar production in patients with subacute sclerosing panenccphalitis (SSPE) has been shown to be directed against antigens of measles virus (Link et al . 1972, Vandvik & NorrbU 1972). In some MS patients antibody production to measles virus has been suggested to occur in the CNS ( S a l m i et al . 1972 a, b). As a preliminary report, we now demonstrate measles-specific antibody activity associated with immunoglobulin fractions of IgG in the cerebrospinal fluid (CSF) from a patient with MS.

Platelet Aggregation Test with Measles Antigen in Multiple Sclerosis

With the measles platelet aggregation test, a new technique recently developed for measuring virus antibody, 153 serum specimens from patients with multiple sclerosis and 164 controls were tested. With one of the three measles antigens used in the test a significantly higher positive rate (P<0·001) was obtained in the specimens from the patients with multiple sclerosis (40%) than in those from the controls (11%). The other two measles antigens also yielded slightly but not significantly higher positive rates in the patients with multiple sclerosis.

The prevalence of multiple sclerosis and some related neuropathological syndromes in south-western Finland. A preliminary report.

As the environment as well as the etnographic structure among people in Finland are quite similar to those in the other Scandinavian countries, we might expect the prevalence rates of multiple sclerosis in Finland to be about the same. The prevalence rates in Scandinavia are quite high; so, Hyllested 1960, gave 641100 000 as the rate in Denmark and, according to Bromma 1960, the corresponding rate was 811100 000 in Gothenburg in 1959. The prevalence rate of 50-60/100000 out of the total population is regarded as a norm (Hyllested), not only in Scandinavia but also in geomedically corresponding regions such as England and the northern parts of North America. Unlike her Scandinavian neighbours Finland has published no epidemiological studies of the prevalence of multiple sclerosis. The area subject to the present study lies in south-western Finland and corresponds to the region of the Central University Hospital of Turku.

E.B. virus and multiple sclerosis.

Coombs test negative. There was a gross deficiency of erythrocyte G-6-PD. The patitnt was transferred to another job. After a month the blood findings had returned practically to normal; the urine contained no urobilin; and the serum bilirubin was 0-5 mg/100 ml. We believe that the acute haemolytic crisis in this patient was due to nalidixic acid. The patient had not eaten broad beans nor taken any haemolysing drugs, nor had he come into contact with any other haemolysing substances in his work. We record this case to draw attention to the importance of G-6-PD-screening in subjects who are occupationally exposed to nalidixic acid or other haemolysing drugs.-We are, etc.,