Comparative study of flucations in the CD4/CD8 ratio in patients
with relapsing-remitting multiple sclerosis treated with Azathioprine or Interferon beta-1a
ZAFIROPOULOS A., XAFENIAS D., ZAFIROPOULOS K., VASILAKI O., XAFENIAS A.,
KOUFOGIANNIS D., TSAVDARIDOU V., AGGOURIDAKI CH., DIMITRIADIS E.A.

It is known that T-lymphocyte cells play an important and crucial regulating role in autoimmune diseases. According to indications that support the view of immunobiologic pathogenicity of multiple sclerosis (MS). we evaluated the fluctuations in the levels of CD4/CD8 ratio of T-lympocytes subpopulations in the peripheral blood of 54 patients who suffered from the relapsing - remitting forms of MS during one year. For this study we examined two groups of patients who suffered from the relapsing - remitting forms of MS. The first group included 30patients, 17 of which were women and 13 men with an average age of 29.5 years, average disease duration from onset of clinical symptoms 4.2 years, as well as average relapse score at EDSS scale 2.4 and average relapse rate 2.2 per year. This group was treated with azathioprine (AZ), 2mg/kgr in two daily doses (bid). The second group included 24 patients, of which 14 were women and 10 men with an average of 28 years, average disease duration from onset of clinical symptoms 4.2 years and average score at EDSS scale 2.9 as well as average relapse rate per year 2.4. The second group was treated with interferon beta-1 (IFN-B), (F1 Rebit 44g 1x3 weekly subcutaneously). The CD4/CD8 ratio was evaluated using flow cytometry. Blood samples were collected monthly and during clinical exacerbation of the disease.

The group treated with IFN-B showed 19 exacerbations, while the grouptreated with AZ showed 32. Increased CD4/CD8 ratio values were manifest in 30 samples of the IFN-B group and in 41 samples of the AZ group. During exacerbations, the study revealed 13 normal and 6 increased values for the IGN-B group revealed, and 11 normal and 21 increased CD4/CD8 ratio values for the AZ group. Similarly, during the remitting period the IFN-B group revealed 247 normal and 24 increased CD4/CD8 ratio values, while the AZ group revealed 313 normal and 20 increased values.

We did not observe a statistically important difference of CD4/CD8 ratio being recorded between the two groups during the relapsing and remitting periods (p=0,29). The two groups showed increased values of CD4/CD8 ratio during the exacerbation of the disease. The AZ group showed a statistically sifnificant difference (p<0.0001), but the IFN-B group did not (p<0.05). An important observation was that the CD4/CD8 ratio increased during the exacerbations in the AZ group, but not in the IFN-B group. This difference was statistically significant (p<0.005). Our results indicated that the increased values of CD4/CD8 ratio do occur more frequently during the exacerbation of the disease in thw AZ group, but not in the az gorup. Our results also revealed lower absolute values of CD4/CD8 ratio during the remissions of the disease regarding the exacerbation periods. The AZ group showed higher absolute values of CD4/CD8 ratio during the exacerbations of the disease, compared with the values of CD4/CD8 ratio during the exacerbations of the disease compared with the period of remission, showing statistically significant difference (p<0,0001). On the contrary, the IFN-B group did not reveal statistically significant difference in the absolute values of CD4/CD8 ratio during remission and exacerbations (p>0.038). Moreover, normal and increased values recorded between the two groups during the relapsing period did not indicate a statistically significant difference. On the contrary, during the remitting period we observed a statistically significant difference between normal and increased values of the two groups. Finally, we did not observe a statistically significant difference between normal and increased CD4/CD8 ratio values between the two groups, neither during the relapsing nor during the remitting period of the disease.

Conclusively, the immunomodulating role of IFN-B treating MS patients suffering from the relapsing/remitting form of the disease gives better results than treating MS patients with AZ. The CD4/CD8 ratio is considered as a main indicator of immunobiologic activity during the course of MS. Our results indicate a better modulation of CD4/CD8 ratio in the IFN-B group compared with the AZ group. Additionally, the IFN-B group reveal a better clinical prognosis than the AZ gorup. Recent studied of simultaneous therapy with IFN-B and AZ in patients suffering from MS showed an improvement of clinical symptoms as well as MRI with the results of MS patients taking a single therapy either with IFN-B or with AZ.

Key words: Multiple sclerosis, CD4/CD8, azathioprine, interferon beta 1-a.