Relationship between rheumatoid factor and the immune response against hepatitis C virus in essential mixed cryoglobulinemia.

OBJECTIVE: The authors examine the relationship between the presence of hepatitis C virus (HCV) and anti-HCV antibodies, rheumatoid factor (RF) activity, the level of complement, and the cryocrit in the sera of patients affected by essential mixed cryoglobulinemia (EMC). In addition, the authors evaluate the circulating B-CD5 positive lymphocytes, believed to be RF producers in the blood of EMC patients. METHODS: Clinical and laboratory data on 219 cases of EMC were collected from five centers of the GISC (Italian Group for the Study of Cryoglobulinemias). Statistical analyses of these data were carried out with the aim of evidentiating significant relationships, in order to shed light on the mechanism of cryoprecipitation. RESULTS: The cryocrit was higher in anti-HCV negative and in HCV-RNA positive sera. The titers of RF activity were significantly higher in anti-HCV negative sera. A linear correlation between RF activity and the cryocrit was observed for HCV-RNA positive cases (r = 0.416), this correlation being highest in the patients who were HCV-RNA positive and anti-HCV negative (0.709). Type III EMC were more reactive than type II against the non-structural antigens of HCV, particularly 5-1-1 and C-22. There were more circulating B lymphocytes sharing membrane antigen CD5 in EMC than in the blood of normals or patients with HCV-related chronic hepatitis. Levels of circulating B-CD5 correlated with serum RF activity (r = 0.677), especially in sera from anti-C-100 negative patients (p = 0.991). CONCLUSION: The data strongly suggest that the level of the cryoprecipitate is a function of both the HCV-RNA in the serum and the RF activity. Antibody specificity against HCV probably influences the density of the cryoprecipitate.

Complement activation in dialysis: effects on cytokines, lymphocyte activation and beta 2 microglobulin.

Anaphylatoxins generated by complement activation by filter membranes are present in plasma during hemodialysis (HD). In the presence of endotoxins which may contaminate the dialysate, they can trigger monocytes to produce interleukin-1 (IL-1) and tumor necrosis factor (TNF), with detrimental effects for the patients. We have investigated whether or not the use of complement activating (cuprophan) and non- (or less-) activating membranes (polysulfone, polymethylmethacrylate or polyacrylonitrile) per se influences cytokine levels in HD patients. Our results indicate that if a sterile bicarbonate solution is used as dialysate, there are no significant increases in IL-1, TNF, interleukin-2 (IL-2) and soluble IL-2 receptors (sIL-2r) throughout HD, even with cuprophan membranes. Moreover even a prolonged use of this membrane (three months) did not change pre-dialysis levels of cytokines and receptors. Use of complement activating membranes also does not influence beta 2 microglobulin levels.

Effect of UVB plus tar therapy on serum levels of interleukin-2 receptors in patients with psoriasis.

Baseline serum levels of interleukin-2 receptor (IL2R) were measured in 65 patients with active psoriasis. IL2R levels in psoriatic patients were significantly higher than in healthy controls (582.4 +/- 289.23 u/ml vs. 369.64 +/- 111.10 u/ml; P less than 0.05), but did not differ statistically from values found in an atopic dermatitis control group (619.88 +/- 254.27 u/ml). Sex, age and severity of the disease do not affect levels of IL2R. The same IL2R levels were measured in 26 psoriatic patients receiving UVB plus tar therapy. This therapy, continued until clinical remission, lowered IL2R levels to values comparable to controls. This decrease may be due to an immunosuppressive effect of therapy.

Periodic acid Schiff (PAS) positivity in fetal erythroblasts.

The smears of 26 fetal blood samples taken for prenatal diagnosis were stained for the PAS reaction. Twelve out of 26 cases were subsequently found to be normal and 14 were found to be affected by different abnormalities; 83.4% of normal cases and 92.8% of abnormal cases showed moderate positivity to the PAS reaction. A higher percentage of PAS positive erythroblasts was found in the abnormal cases (p less than 0.01). Five cases with a percentage greater than 10% also showed a very high percentage of erythroblasts. No linear correlation was found between PAS positivity and erythroblastosis either in the normal or the abnormal cases, but pooling them resulted in a correlation between PAS positivity and erythroblastosis (r = 0.536; p less than 0.005). PAS positivity was most often diffuse and scored 1+. Since erythroblastosis is considered an indirect sign of fetal liver erythropoiesis, the hepatic environment and its peculiar hemopoiesis could play a role in producing a cohort of PAS positive erythroblasts.

T lymphocyte subpopulations in myelodysplastic syndromes.

T cell subpopulations, defined by monoclonal antibodies (OKT3, OKT4 and OKT8), were assessed on 13 patients with myelodysplasia (MDS). The percentage and numbers of OKT3- and OKT4-positive lymphocytes were significantly lower (p less than 0.025) than in normal controls, whereas those of OKT8 were not. In the group of patients with refractory anemia with excess of blasts (RAEB) and in those with chronic myelomonocytic leukemia, the percentage and absolute numbers of OKT8 lymphocytes were significantly lower (p less than 0.025) than in patients with refractory anemia or with primary acquired sideroblastic anemia, while those of OKT3 and OKT4 did not differ significantly. Quantitative impairment of T cell subpopulations may be part of the myelodysplastic situation as a result of the dyslymphopoiesis, according to the hypothesis that MDS originate from pluripotent stem cells. The decrease of OKT8 in RAEB and chronic myelomonocytic leukemia could be related to the previously shown insufficient erythropoietic activity in these patients.

A comparative study on peripheral blood lymphocyte subpopulations in different kinds of warts.

Peripheral blood T-cell subpopulations were evaluated in 36 patients with clinically different types of warts, subdivided in 4 groups (common, genital, flat and plantar warts). A significant decrease was found in OKT3 and OKT4 subsets total count and in OKT4/OKT8 ratio in patients with common and genital warts as compared with controls. Only in common and genital warts did we also observe a significant decrease of percentage of OKT4 subset. No significant difference of considered parameters was observed in flat and plantar warts as compared to controls, apart from a significant increase in number of OKT8 subset in flat warts. We then discuss this different status of C.M.I. in patients with different clinical warts, stressing the importance of various types of HPV.

Peripheral blood lymphocyte subpopulations in patients with viral warts.

Peripheral blood T-cell subpopulations were evaluated in 32 patients affected by viral warts and in 32 unaffected individuals belonging to a control group. A significant decrease was found in total lymphocytes as well as OKT3 and OKT4 subsets among affected patients. A significant negative correlation was also found between OKT3 and OKT4 numbers as well as OKT4/OKT8 ratio and duration and extent of lesions. A significant positive correlation was found between the duration and the extent of lesions and the percentage of OKT8 subsets, but not the total number of OKT8. These data confirm that a cell-mediated immune deficiency is present in patients with viral warts. We then discuss whether the decrease of cellular immunity in these patients is a primary event or, rather, the result of persistent verrucosis.