Performance Evaluation and Clinical Associations of Immunoassays That Detect Antibodies to Negatively Charged Phospholipids Other Than Cardiolipin.

OBJECTIVES: We evaluate the performance characteristics of antiphosphatidylserine (anti-PS), antiphosphatidylinositol (anti-PI), and antiphospholipid mixture (APhL) enzyme-linked immunosorbent assays (ELISAs) compared with anticardiolipin (aCL) and anti-ß2 glycoprotein I (anti-ß2GPI) in a large group of patients with antiphospholipid (aPL)-related diseases. METHODS: Serum samples from 548 patients from the Hopkins and Jamaican systemic lupus erythematosus cohorts, the PROMISSE cohort, and the Antiphospholipid Standardization Laboratory were examined for immunoglobulin G (IgG)/immunoglobulin M (IgM) positivity in aCL, anti-ß2GPI, anti-PS, anti-PI, and APhL ELISA assays. RESULTS: All IgG assays were associated with one or more thrombotic and/or obstetric manifestations, with an increased risk associated with higher antibody titers. Analytical performance was similar among assays, but IgG assays performed better than IgM counterparts. CONCLUSIONS: Increasing titers of APhL, anti-PS, and anti-PI antibodies could indicate an increased risk of thrombotic and/or obstetric aPL-related manifestations. These assays may be promising biomarkers for particular APS manifestations.

HLA-DRB alleles and systemic lupus erythematosus in Jamaicans.

BACKGROUND: The human leukocyte antigens (HLA) are associated with susceptibility to systemic lupus erythematosus (SLE) and manifestations of SLE in different ethnic groups. METHODS: A DNA-based HLA-typing method was used to determine alleles of HLA-DRB1, DRB3, DRB4 and DRB5 in Jamaican patients. A total of 70 patients and 100 control subjects were studied. RESULTS: HLA-DRB3*01/03 was significantly associated with susceptibility to SLE, while DRB1*15/16 was associated with the presence of oral ulcers in patients with SLE. The haplotype DRB1*13/14.DRB3*01/03 was also more frequent in SLE patients. No other significant associations were found. CONCLUSION: The SLE HLA associations in Jamaicans differ from those in other black populations.

Arthritis in Jamaica - abstract

Presented are data on 241 patients who attended the Rheumatology Clinic U.H.W.I. over a 5-month period. Two hundred and eight (86 percent) of the patients were female. The ages ranged from 7 to 87 years (mean 41 years). Seventy-eight (32 percent) had rheumatoid arthritis. Their mean age was 47 years (range 18-84 years). Only 2 patients were male. Twenty-one (27 percent) were negative for the rheumatoid factor, and 7 (9 percent) had anti-nuclear antibodies. Twenty-seven patients (11 percent), all female, were diagnosed as having systemic lupus erythematosus. Their mean age was 30 years (range 10-50 years). Two patients were consistently negative for anti-nuclear antibodies. Other diseases frequently diagnosed were: degenerative joint disease in 26, juvenile rheumatoid arthritis in 12, mixed connective tissue disease in 8, spondylitis in 7. Forty-one patients were seen with arthralgia and/or myalgia without evidence of an inflammatory process (AU)

Abnormal haemorrheological changes in systematic lupus erythematosus (SLE) [abstract]

Vascular complications are frequently associated with SLE. It is hypothesized that haemorrheological abnormalities may play a role in the aetiology of micro-and-macrocirculatory disorders in SLE. The range of rheological abnormality was determined by measuring the concentration of plasma fibrinogen, serum albumin and relating these abnormalities to change in relative plasma viscosity (RPV) and relative serum viscosity (RSV) in 21 SLE patients. The SLE disease activity index (SLEDAI) was used to define the severity of the disease. Eleven patients were "severe" (SLEDAI score> 12) and ten patients were "limited" (SLEDAI score< 12). RPV and RSV were measured by capillary viscometry. Plasma fibrinogen was determined by a clot-weight procedure and serum albumin and globulin by the Biuret method. Results from the SLE patients were compared with those from a randomly selected control group. A significant increase in RPV (p< 0.001) and RSV (p< 0.05) was recorded for the SLE patients. The patients with severe disease had a significant (p<0.001) increase in RSV but neither in fibrinogen nor RPV as compared with patients with limited disease activity. The increased viscosity in SLE patients may constitute an impediment in blood flow. Furthermore, the higher serum viscosity in patients with severe disease suggests that serum viscosity may provide a useful marker for disease activity. (AU)

Arthritis in childhood: a report on 65 consecutive cases observed at the University Hospital of the West Indies

In a two-year period (October 1985 - September 1987), 65 children presented to the Child Health Department and/or rheumatology clinic at the University Hospital with arthritis. Eighteen children (28 percent) had juvenile chronic arthritis, ten (15 percent) rheumatic fever, eight (12 percent) systemic lupus erythematosus and thirteen (20 percent) had self-limiting arthritis. Systemic onset of juvenile chronic arthritis occurred only in one child; nine children has polyarticular and eight pauci-articular onset of disease. The self-limiting arthritis was difficult to differentiate from juvenile chronic arthritis; therefore serological testing for bacterial and viral infections should be performed before anti-rheumatic therapy is undertaken. Arthritis in childhood is not uncommon in Jamaica. However, the outcome appears to be generally favourable except in a few cases of juvenile chronic arthritis (AU)

Histoplasmin sensitivity among cavers in Jamaica

Histoplasmin skin tests were conducted on a group of 30 Europeans residents in Jamaica. Ten subjects with no exposure to a guano-cave environment showed a negative response to the test. Two of eight subjects who had made only a single cave visit showed positive reactions. All twelve subjects with a history of frequent visits to guano-caves showed a positive response. The significance of these data to local levels of histoplasmin sensitivity and the ocurrence of cave-mediated outbreaks of histoplasmosis are discussed (AU)

Arthritis in childhood: report of 61 consecutive cases seen at the University Hospital of the West Indies - abstract

A two-year survey (October'85 - September'87) was undertaken to determine the pattern of arthritides in children presenting to the Child Health Department, and/or Rheumatology Clinic, at the University Hospital. There were 61 children (24 males, 37 females) aged from one to sixteen years, with a median age of ten years. The duration of follow-up ranged from one month to nine years. Seventeen (28 percent) children were diagnosed as juvenile chronic arthritis. A polyarticular onset was seen in 9/17 children, pauci-articular onset in 7/17 children and one child had a systemic onset. The most commonly affected joint was the knee (25 percent), followed by small joints of the hand (19 percent). Residual joint dysfunction was mild in 8 children and severe in 2. The remaining 7 children had no functional abnormalities at the time of last review. Nine (15 percent) children had arthritis associated with rheumatic fever, without evidence of carditis. Seven (11 percent) children were diagnosed as systematic lupus erythematosus (SLE). The main features of SLE in addition to arthritis were skin rashes, fever and generalised lymphadenopathy. Renal involvement was seen in 2 children. Two children with SLE also had homozygous sickle-cell disease. A self-limiting type of arthritis was seen in 13 (21 percent) children. Three (5 percent) had septic arthritis and another three had Kawasaki disease. Nine had other types of arthritides. Arthritis in childhood is not uncommon in Jamaica. However, the outcome appears to be generally favourable except in a few cases of juvenile chronic arthritis (AU)

Stilboestrol and stuttering priapism in homozygous sickle-cell disease - abstract

The vaso-occlusive process in sickle-cell disease compromises drainage of the corpora cavernosa and may cause priapism. This may consist of short, recurrent, nocturnal, "stuttering" attacks or major episodes lasting over 24 hours and usually resulting in impotence. Stuttering attacks have been reported in approximately 40 percent of adults with SS disease and, in at least one-quarter of the patients, herald a major episode. The therapy of stuttering attacks is unsatisfactory, and there are unconfirmed anecdotal reports that oral stilboestrol may be effective. A double-blind cross-over controlled study has therefore been performed in 11 patients with SS disease and stuttering priapism. Patients were randomised to either tablet A (placebo) or tablet B (stilboestrol, 5 mg), taken daily for 2 weeks. A calendar of priapism was recorded and if attacks did not cease, patients were crossed-over to the alternative modality for a further 2 weeks. The results showed that the placebo failed in all cases and that stilboestrol inhibited attacks in all 9 patients completing the study. The results were highly significant (Fishers exact test, p<0.001), indicating that oral stilboestrol is effective in terminating attacks of stuttering priapism (AU)

Stilboestrol and stuttering priapism in homozygous sickle-cell disease

A double-blind, placebo-controlled crossover study was conducted in 11 patients with stuttering atacks of priapism and homozygous sickle-cell (SS) disease. Stilboestrol 5 mg daily was better than the placebo in preventing attacks (AU)

Glomerular function and hyperuricaemia in sickle cell disease

Renal insufficiency is common in adults with homozygous sickle cell disease, and the contribution of glomerular failure to the hyperuricaemia which is often a feature of the disease has therefore been investigated. In a study of 64 patients between the ages of 15 to 66, serum urate concentration was dependent on renal urate clearance and also on creatinine clearance. The relation between serum urate and creatinine clearance was abnormal in patients with sickle cell disease and it is suggested that this might be caused by high single nephron glomerular filtration rates. Both the amount of urate excreted per millilitre of glomerular filtrate and the fractional excretion of urate increased with falling creatinine clearance, suggesting that the ability to increase tubular urate secretion was preserved. Patients with extensive tubular disease as shown by tubular proteinuria had serum urate concentrations which were not significantly different from those of age and sex matched non-proteinuric patients. Evidence that renal tubular disease interferes with urate secretion and causes hyperuicaemia in patients with sickle cell disease needs to be reinterpreted in the light of these findings.(AU)

The immunological profile of babies with homozygous sickle cell disease - abstract

Seventy-two babies with homozygous sickle cell disease (SS) and age-matched controls with a normal haemoglobin were screened for immunoglobulin and complement abnormalities at birth, and again at 6, 12, 18 and 24 months of age. Twenty-seven SS babies had more than one sample taken at different intervals. Abnormalities of IgG, IgA, C3 and C3d were all detected in SS patients at the age of 2 years or before. As a group, elevations of IgA (p<0.05) and of complement breakdown product levels (p<0.002), were apparent from the age of 6 months onwards. As the immunological abnormalities occur at a time when the majority of infections in SS children are observed, it is suggested that they may contribute to the increased susceptibility to infection in SS disease (AU)

Mononuclear cell populations in sickle cell disease - abstract

Susceptibility to a variety of infections is well-recognised in patients with homozygous sickle cell (SS) disease and is generally attributed to loss of splenic phagocyte function and impaired complement fixation. A possible contribution from abnormal numbers or function of mononuclear cells has not been previously investigated. Studies on lymphocyte and monocyte populations 22 patients with SS disease and in 25 controls with a normal haemoglobin genotype are therefore presented. The total numbers of lymphocytes in peripheral blood samples was significantly higher (p<0.001) in SS patients compared to controls (mean ñ SD: 3.29 ñ 0.98 vs 2.24 ñ 0.78 X 10 9/1). When expressed as a percentage of total lymphocyte population, B-cells were normal and T-cells reduced in SS disease but when expressed in absolute numbers both T-cells and B-cells were significantly increased (p<0.01 and p<0.05 respectively). Lymphocyte transformation following stimulation with phytohaemoglutinin and conconavalin A was normal but was significantly increased (p<0.02) after stimulation with pokeweed mitogen. The total number of monocytes in the peripheral blood was higher (p<0.00) in SS patients than in controls (0.86 ñ 0.45 vs 0.23 ñ 0.12 X 10 9/1) and the percentage of nonocytes in the mononuclear cell isolate was increased in SS disease, as judged by morphology (p<0.001) and capability to phagocytose latex particles (p<0.005). The studies do not indicate a major cellular immune defect in patients with SS disease (AU).

Haematological and immunological studies of recurrent infections in homozygous sickle cell disease - abstract

The increased susceptibility in patients with homozygous sickle cell (SS) disease has been ascribed to defects in splenic function, immunoglobulin abnormalities and complement deficiencies. In the hope of finding prognostic factors in such patients, serum complement and immunoglobulin levels were studied in 19 SS patients who subsequently developed multiple serious infections and compared with those in 19 age matched SS controls without infectious complications. Haematological parameters of both groups at age 6 months, 1 year and 2 years and the pitted red cell count which is a measure of splenic function, were also compared. Complement, immunoglobin levels, total haemoglobin, HbF, reticulocyte and bilrubin levels were similar in both groups. The pitted red cell count was significantly lower in the control patients without bacterial infections (0.01). It is suggested that an elevated pitted red cell count may be a baluable indicator for susceptibility to infections in SS disease (AU)

Mononuclear cells in sickle cell disease: subpopulations and in vitro response to mitogens

The subpopulations of mononuclear cells and the lymphocyte proliferative capacity following mitogen stimulation were studied in 22 patients with homozygous sickle cell (SS) disease and 25 controls with a normal haemoglobin (AA) genotype. The total number of lymphocytes in peripheral blood samples was higher in SS patients compared to controls. Expressed as a percentage of total lymphocytes, the number of B lymphocytes (detected by membrane immunoglobulin Fluorescence) was normal and of T lymphocytes (identified by sheep erythocyte rosetting) was slightly reduced in SS disease. Expressed in absolute numbers, both B and T lymphoctes were increased. Lymphocyte proliferation measured by tritium labelled thymidine incorporation following stimulation with phytohaemaeglutin A and concanavalin A was normal. Following pokeweed mitogen stimulation, thymidine incorporation was significantly increased in SS disease although normal when expressed as a stimualtion index. These results do not suggest a major defect in cell mediated immunity in sickle cell disease. The number of circulating monocytes was increased in SS disease and correlated inversely with the number of reticulocyytes (r= -0.58, p < 0.005) (AU)

Primary antiphospholipid syndrome: a case report

A case of the primary antiphospholipid syndrome (PAPS) in a 21-year-old Jamaican female is described. Recurrent abortions, thrombocytopenia and neurological complications as well as lupus anticoagulant positivity in the absence of features of systemic lupus erythematosus (SLE) were the main clinical findings. Diagnostic criteria, treatment and prognosis are discussed. When the antiphospholipid syndrome (APS) is present in the primary form, the diagnosis may be difficult but its recognition may prevent those vascular events which can lead to significant morbidity and foetal wastage (AU)

Mortality of Jamaican patients with systematic lupus erythematosus

A retrospective study of all patients with systemic lupus erythematosus (SLE) who died at the University Hospital of the West Indies over a 14-year period is presented. The major cause of death was infection followed by renal failure. Gram-negative organisms were the major microbiological agents causing infections. Side-effects of therapy were common, in particular bone marrow depression and haemorrhage related to anticoagulants. It appears that controlling severe lupus activity without increasing the risk of life-threatening complications remains an important goal in the treatment of SLE.(AU)

Infective arthritis due to Blastocystis hominis

A patient with rheumatoid arthritis taking prednisone developed Blastocystis hominis acute diarrhoea, which was associated with increased inflammation and effusion of the left knee. B. hominis organisms were found in synovial fluid from the left knee. The patient responded dramatically to metronidazole treatment. B. hominis may become disseminated in immunosuppressed patients with diarrhoea and may cause infective arthritis. (AU)

Serum immunoglobulin levels in children with homozygous sickle cell disease

Serum immunoglobulin levels (IgA, IgG, and IgM) have been assayed in a representative sample of children (aged 1-7 years) with homozygous sickle cell disease and in age/sex-matched control children with a normal haemoglobin genotype, followed from birth in a prospective cohort study. In SS disease, significant elevation of IgA occurred from the age of two years and of IgG from the age of six years. IgM levels were not significantly different in the two genotypes. The mechanisms contributing to these changes in immunoglobulins are currently unclear as is their clinical significance.(AU)

Primary antiphospholipid syndrome: a case report

A case of the primary antiphospholipid syndrome (PAPS) in a 21-year-old Jamaican female is described. Recurrent abortions, thrombocytopenia and neurological complications as well as lupus anticoagulant positivity in the absence of features of systemic lupus erythematosus (SLE) were the main clinical findings. Diagnostic criteria, treatment and prognosis are discussed. When the antiphospholipid syndrome (APS) is present in the primary form, the diagnosis may be difficult but its recognition may prevent those vascular events which can lead to significant morbidity and foetal wastage.

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)