IMMUNOLOGICAL PARAMETERS AND SEVERITY OF SICKLE CELL ANAEMIA IN NIGERIAN ADULTS

Abstract

Remarkable individual variabilities occur in the manifestations of sickle cell anemia, but the possible contribution of the immune status to this has not been previously evaluated. Selected immunological parameters were evaluated in 113 Nigerians aged between 16 and 39 years that have (HbSS) disease. Seventy (70) apparently Healthy Nigerians of comparable age, sex and socioeconomic status (SES), but of haemoglobin genotype AA served as controls. The HbSS subjects were further separated into three severity groups, mild, moderate and severe. These groupings were made based on information obtained from clinical examination, haemoglobin concentration (to assess degree of anaemia), review of patients’ hospital records to ascertain crisis-rate (average number of crisis/year) and number of complications of sickle cell anaemia which the patients have had. Scores attained for degree of anaemia, crisis-rate. and number of complications were summed-up to derive the total severity score or severity index for each HbSS subject. The mild group corresponded with those whose severity index was <=3; moderate >3 but <=7; and severe, > 7. Comparison of the immunological parameters was made between the control group and the various severity groups as well as between one severity group and another. The relationship between each immunological parameter and crisis rate, number of complications, and severity index was determined. The phagocytic competence of neutrophils of the various severity groups as indicated by their number and ability to reduce nitroblue tetrazolium (NBT) dye, was adequate. Neutrophils of the mild and moderate groups did not differ significantly from those of the control group in their candidacidal activity (CA) but marked impairment of this function was observed in the severe group. CA was found to be inversely related to crisis rate (r=-0.46 P<0.001), number of complications (r= 0.52, p<0.001), and severity index (r= 0.5, P<0.001). The functional integrity of the classical complement pathway (CH50), C3 and C4 protein levels were not significantly different in any severity group compared to the control group. Circulating immune complex (CIC) levels were significantly elevated in the moderate and severe groups in relation to controls. This parameter manifested a significant positive association with the number of complications (r=0.28, P<0.02). The functional intergrity of the alternative complement pathway (AP50), in relation to the control group, was significantly diminished in the various severity groups. AP50 was significantly inversely related to crisis-rate (r= -0.31, P< 0.01) and severity index (r=-0.25, P<0.05), but did not show a significant relationship with the number of complications (r=-0.08, P>0.1). Alternative pathway factor B (Bf) levels were comparable between all groups. Of the acute phase reactants quantified, albumin, and d2-Macroglobulin did not show significant variations. Transferrin (Tf) and haptoglobin (Hp) on the other hand, were markedly reduced in the HBSS groups (P<0.001) whereas alpha- 1-antitrypsin (AIAT), C- reactive protein (CRP) and caeruloplasmin were markedly elevated (P < 0.001). Only Tf and CRP however showed significant correlations with the various indices of severity. Immunoglobulin G, A and M classes were significantly higher in the HbSS groups compared to the control group (P<0.001 for IgG and IgM; P<0.01, for IgA). Similarly, IgG1 and IgG3 subclasses ware significantly higher in the HbSS groups than in controls (P<0.02; P<0.005, respectively). IgG3 showed a significant relationship with frequency of crisis (r=0.44; P<0.05). Assessment of T and B lymphocyte, as well as null-cell populations by the rosette techniques showed that percentages of B-lymphocytes were comparable between all the groups. Conversely the percentages of T lymphocyte and null cells were significantly diminished and elevated, respectively, in the moderate and severe Hb5S groups. Whereas the percentages of T Lymphocytes were inversely related to crisis-rate (r= 0.35, p<0.01), number of complications (r= 0.45, P<0.001) and severity index (r=0.46, P<0.001), the percentages oF null cells showed positive associations with crisis rate (r=0.32, P<0.001, complications and severity index (r=0.46, P<0.001) (r=0.44, P<0.00I). An apparent discordance was observed specifically as it relates to T and null-cells when these cells were similarly assessed after being quantified by using anti-CD4, CD6, CD8 and CD19 monoclonal antibodies. Although serum E-rosette inhibitory substance (ER-IS) occurred at comparable frequencies in the HbSS (17.2%) and control (8%) groups (X 2=2.3858, P>0.2), those HbSS subjects with ER-IS had significantly higher mean levels of circulating immune complexes (CICS) and lower mean percentages of E-rosetting lymphocytes. Thus ER- IS and CICs were speculated to contribute to the observed discrepancy in the T - cell population estimated by E - rosetting and by use of monoclonal antibodies. It is concluded that the study described in this thesis has provided hitherto unavailable information on the immunological status of Nigerian sickle cell a subjects, revealing certain parameters that are deranged. Some of these deranged parameters, specifically, CA, AP5O, CRP, Tf, CICs and E- rosetting lymphocytes appear to be correlates of severity in this disease. These findings have potential therapeutic as well as predictive value in sickle-cell anaemia.