The significance of immune disorder in tropical spastic paraparesis

The reports of the occurrence of HTLV-1 infection and/or HTLV-1 associated myelopathy (HAM)/tropical spastic paraparesis (TSP) in patients with certain organ-specific and nonorgan-specific autoimmune diseases prompted us to assess the relationship between TSP and humoral autoimmunity. Blood samples from 76 TSP patients, 60 asymptomatic HTLV-1 carriers and 100 HTLV-1 seronegative blood donors were examined for the presence of organ-specific and nonorgan-specific autoantibodies, reactive serological tests for syphilis, immunoglobulin and complement concentrations as well as immunecomplexes. High prevalences of autoantibodies (39/76, 51 percent), reactive serological tests for syphilis (23/76; 30 percent), hypergammaglobulinaemia (69/76, 90 percent) and the complement fixing immune complexes (44/76, 58 percent) were found in the TSP patients. These indicators of immunological disorder were found in statistically significantly lower prevalences in asymptomatic HTLV-1 carriers (12/60, 20 percent; p < 0.001; 6/60, 10 percent; p < 0.05; 32/60, 53 percent; p < 0.001 and 8/60, 13 percent; p < 0.001, respectively) and HTLV-1 seronegative blood donors (8/100, 8 percent; p < 0.001; 3/100, 3 percent; p < 0.001; 15/100, 15 percent p < 0.001 and 5/100, 5 percent; p < 0.001, respectively). The profiles of autoimmune phenomena observed in the patient and control groups revealed that they were associated with TSP rather than mere HTLV-1 infection and consequently pathogenic significance. The array of immunological features present in TSP was suggestive of autoimmune disease resulting from immune dysfunction. Studies which explore the possible existence of HTLV-1 induced autoantibodies with specificity for antigens of the spinal cord in TSP might be useful in elucidating its pathogenesis.(Au)

Recurrent infections in sickle cell disease: haematological and immune studies

Some haematological and immunological indices were compared in 19 children with sickle cell disease and a history of recurrent infections and in 16 children with sickle cell disease without any known infections. The recurrent infection group had significantly greater pitted red cell counts and greater absolute monocyte counts. No differences were apparent in routine haematological indices, foetal haemoglobin, immunoglobulin, or complement levels between the groups. The interpretation of these results is discussed (AU)

Plasma haemoglobin and complement activation in sickle cell disease

The role of haemolysis in producing deficient complement function in homozygous sickle cell disease was studied by measuring indices of complement activation and of haemolysis in 30 asymptomatic patients. Plasma concentration of C3d (an index of increased C3 turnover) was elevated in 40 percent of patients and modest decreases in serum concentration of C3 and functionally (haemolytically) active factor B were found. There was a positive correlation between C3d and plasma haemoglobin concentration (r = 0.56, p less than 0.005). Reticulocyte count and foetal haemoglobin concentration also contributed to variation in C3d, though to a lesser extent than plasma haemoglobin. Intravascular haemolysis in sickle cell disease may produce activation of complement and thus cause partial depletion of functional factor B and C3. This may reduce the immune function of the alternative pathway. (AU)

Dengue fever in Jamaica with shock and hypocomplementaemia, haemorrhagic, visceral and neurological complications

Ten patients with severe dengue syndrome have been seen in the recent epidemic in Kingston, Jamaica. Two patients had dengue shock syndrome. One had abnormal coagulation indices and another had severe haemorrhagic diarrhoea. Five patients had neurological syndromes of whom 3 had encephalitis, one had a meningoencephalomyelitis and one had a post-infective type demyelination syndrome. Hepatitis occurred in 2 patients, one of whom had dengue haemorrhagic fever. Pancreatitis occurred in 2 patients, one of whom had haemorrhagic fever. Concentrations of several components of serum complement were reduced only in patients with dengue shock syndrome and not in those with other complications. Although altered dengue syndromes have occurred aginst a background of multiple dengue virus types, the incidence is much lower than occurs in South-East Asia, no definite fatalities have been confirmed and adults seem to have been primarily affected rather than children (AU)

In vitro synthesis of humoral factors (immunoglobulins and complement) in lesional skin of leprosy patients

Reviews the leprosy situation in the world and in Suriname, as well as its clinical forms and immunological aspects. Skin samples with a diameter of 6 mm were taken from untreated lepers, 3 samples per patient. The aims were: to determine whether humoral factors are synthesized in the skin lesions of lepers, to study cells producing immunoglobulins and complement, and to study whether the locally synthesized immunoglobulins have antibody activity against M. leprae. The in vitro culture technique (Hochwald 1961/ Furth 1966), the direct immunofluorescence technique and the crossed immuno-electrophoresis with intermediate gel (Axelsen/Week;1973) were used. It was shown that lesional skin of indeterminate leprosy does not synthesize immunoglobulines. However, IgG was synthesized in tissue cultures of other leprosy varieties. Ig-positive cells were found in some of the patients examined, whereas complement-positive cells were not found. Culture fluid did contain newly synthesized antibodies against different M. leprae antigenic components. These antibodies were also found in the sera of the patients examined. This showed that antibody synthesis does not take place in the skin lesions, but elsewhere in the body. The biological significance of these antibodies is not yet known. Further study is needed to throw light upon this problem

Systemic lupus erythematosus and sickle-cell anaemia

In view of the relationship between immunity deficiency states and immune complex diseases such as systemic lupus erythematosus (SLE) a possible association between SLE and sickle-cell disease, in which there is evidence of immunity deficiency, is of interest.(AU)

Deficiency of factor B of the complement system in sickle cell anaemia

Factors B and D as well as the total activity of the alternative pathway of complement activation were measured using a functional assay in sera from 29 patients with sickle cell anaemia and 18 normal controls. Total alternative pathway activity was reduced in the patients compared with controls. In patients with abnormally low total alternative pathway activity factor D levels were normal, whereas factor B levels were significantly depresed to a mean level of about half of normal. Regression analysis in patients also showed a singnificant relation between total alternative pathway activity and factor B levels. A deficiency of factor B is the likely cause of the defect in the complement system in patients with sickle cell anaemia. Such a defect may contribute to the excessive proneness of such patients to severe infection.(AU)

Complement activation in asymptomatic patients with sickle cell anaemia

Previous reports have suggested that a defect in serum complement may contribute to the increased susceptibility to infection shown by patients with sickle cell anaemia (SCA). In order to define the nature of any complement abnormality in SCA, we investigated the complement system in eighty-seven patients during asymptomatic periods, and analysed factor B turnover in a small sample. In these patients geometric mean serum concentrations of functionally active factor B and factor D, and of C3 and C4 protein (expressed as a percentage of normal reference serum) were lower than in controls (78 percent vs. 107 percent, P<0.001, 86 percent vs. 103 percent, P<0.001, 91 percent vs. 100 percent, P<0.01, 89 percent vs. 105 percent, P<0.05 respectively). The ratio of the serum concentration of functionally active factor B to factor B protein was lower in patients than in controls (mean 75 percent s.d 16 percent vs. mean 93 percent, s.d 22 percent P<0.001), indicating a functional deficiency of factor B protein. In addition, the fractional catabolic rate of radiolabelled factor B was markedly increased in four out of seven asymptomatic patients studied, and was inversely related to the functional factor B concentration in serum (r=-0.59, P<0.05); factor B synthesis was uniformly increased. Complement activation was not related to the presence of circulating Clq binding material. We conclude that complement activation, rather than defective synthesis as previously suggested, contributes to the abnormalities in complement component concentration and function in asymptomatic subjects with sickle cell anaemia (Summary)

The effect of lactoferrin, an iron-binding protein on complement activity

The effect of Lactoferrin (LF) on complement activity has been studied using the sheep red blood cell - haemolysin system. Although Lactoferrin itself is devoid of complement activity, it does affect complement action. In the absence of 2 C50 units of complement, lysis occurs, the amount observed depending on the ratio of complement to Lactoferrin used. C1 was shown to be the target for Lactoferrin action, since the inhibition of lysis produced by 500 ug of Lactoferrin, could be completely reversed by crude C1.C3, a contaminant of this crude preparation, had no such effect. Investigations to establish the specific effect of Lactoferrin on C1 indicate that Lactoferrin is a potent activator of C1, since a six-fold increase in C1 activity results when they are mixed together. These observations are consistent with the hypothesis, that Lactoferrin exerts an influence on the complement system, as a result of its capacity to activate C1. (AU)