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Biomedical subjects

M L Boey

Publications and source records attributed to M L Boey.

At least 55 records · Page 3Linked to original sources

HLA class 2 genes in Singaporean Chinese rheumatoid arthritis.

This study analysed HLA class 1 and 2 allele associations in Singaporean Chinese patients with RA. Seventy patients (ARA definite or classical) and 80 controls were typed for HLA class 1 alleles by serology and class 2 alleles by serology and the PCR/SSO method. RA patients had higher frequencies of DRB1*0405 (40 vs 12.5%; corrected probability value (PC) < 0.02, relative risk (RR) = 4.7, 95% confidence limit (CL) 2.1-10.6), DRB1*1001 (14.3 vs 1.3%; PC = 0.06, RR = 13.2, 95% CL 1.6-105.7), DQB1*0401 (38.6 vs 12.5%; P = 0.006, RR = 4.4, 95% CL 1.9-10.0) and DQB1*0501 (20 vs 5%; PC = 0.048, RR = 4.8, 95% CL 1.5-15.2). It is concluded that Chinese RA is associated primarily with HLA DRB1*0405 and DRB1*1001 which share common amino acid sequences in the third hypervariable region of the DR beta chains shown to be associated with RA in other ethnic groups. Patients without DRB1*0405 and *1001 had a higher frequency of DRB1*0901, which is in linkage disequilibrium with HLA B46 in the Chinese.

Adolescent↗

The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus.

To gain insight into the mechanisms of autoantibody induction, sera from 40 patients with systemic lupus erythematosus (SLE) were tested by ELISAs for antibody binding to denatured individual histones, native histone-histone complexes, histone-DNA subnucleosome complexes, three forms of chromatin, and DNA. Whole chromatin was the most reactive substrate, with 88% of the patients positive. By chi-square analysis, only the presence of anti-(H2A-H2B), anti-[(H2A-H2B)-DNA], and antichromatin were correlated with kidney disease measured by proteinuria > 0.5 g/d. SLE patients could be divided into two groups based on their antibody-binding pattern to the above substrates. Antibodies from about half of the patients reacted with chromatin and the (H2A-H2B)-DNA subnucleosome complex but displayed very low or no reactivity with native DNA or the (H3-H4)2-DNA subnucleosome complex. An additional third of the patients had antibody reactivity to chromatin, as well as to both subnucleosome structures and DNA. Strikingly, all sera that bound to any of the components of chromatin also bound to whole chromatin, and adsorption with chromatin removed 85-100% of reactivity to (H2A-H2B)-DNA, (H3-H4)2-DNA, and native DNA. Individual sera often bound to several different epitopes on chromatin, with some epitopes requiring quaternary protein-DNA interactions. These results are consistent with chromatin being a potent immunogenic stimulus in SLE. Taken together with previous studies, we suggest that antibody activity to the (H2A-H2B)-DNA component signals the initial breakdown of immune tolerance whereas responses to (H3-H4)2-DNA and native DNA reflect subsequent global loss of tolerance to chromatin.

Animals↗

Antihistone antibodies in systemic lupus erythematosus: assay dependency and effects of ubiquitination and serum DNA.

OBJECTIVE: Antihistone antibodies occur in systemic lupus erythematosus (SLE) but there are many discrepancies in their reported prevalence, isotype, specificity and correlation with disease symptoms. We examined the role of the assay and the influence of serum DNA as possible causes of these discrepancies. In addition, we sought to confirm the presence of antibodies to ubiquitin and ubiquitinated H2A (uH2A). METHODS: Western blot and enzyme linked immunosorbent assay (ELISA). RESULTS: Sera displayed substantial differences between ELISA and Western blot in reactivity to individual histones when all reagents were nearly identical, indicating that subtle differences in the solid phase adsorbents have pronounced effect on histone antigenicity. No uniform pattern of antibody reactivity with the 5 histones was apparent with either assay. For most sera, digestion with DNase caused only minor decrease in binding to histones and no histone class showed particular sensitivity to this treatment. In agreement with most other studies, no significant correlation between histone binding and symptoms was found. Just 2 of 40 sera showed detectable binding to ubiquitin or uH2A. CONCLUSION: Although IgG antihistone antibodies were detected in 53-55% of patients with SLE with active disease, the sensitivity of antibody activity to assay conditions, patient variability, and lack of correlation with symptoms compromise the clinical utility of measuring antihistone antibodies by Western blot or ELISA: We were also unable to confirm that ubiquitin and uH2A are major antigens recognized by antibodies in SLE.

Adult↗

Lipid profiles in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of abnormal lipid profiles in 100 consecutive patients with systemic lupus erythematosus (SLE) and the role of potential risk factors. METHODS: Fasting lipid profiles were measured using an enzymatic method. Biodata noted for each patient included age, sex, race, presence of diabetes mellitus, thyroid disease, familial hyperlipidemia, smoking history, presence of nephritis or nephrotic syndrome, lupus activity as measured by the lupus activity criteria count (LACC), duration of SLE, use of antihypertensive agents and the current and cumulative dose of steroids. Statistical analysis was done using PC SAS software. RESULTS: Seventy-three patients had abnormal lipid profiles. Patients with normal and abnormal profiles were comparable in age, sex, race, history of diabetes mellitus, familial hyperlipidemia, and smoking. Abnormal values of total cholesterol (TC), low density lipoprotein (LDL), triglycerides (TG) and TC/high density lipoprotein (HDL) were associated with renal involvement and high dose corticosteroids (> 30 mg prednisolone/day). HDL levels were significantly lower in patients receiving high dose corticosteroids (p < 0.05). In patients with active lupus disease but without renal disease, lipid abnormalities were not observed. CONCLUSION: Abnormal lipid profiles are common in this group of patients with SLE. High dose steroids and the nephrotic syndrome are important contributing factors.

Adult↗

Late onset lupus: a clinical and immunological study in a predominantly Chinese population.

OBJECTIVE: To compare retrospectively the clinical, laboratory, and immunological features between 50 patients with early and 26 with late onset (> 50 years old) systemic lupus erythematosus (SLE) and to observe differences between our predominantly Chinese and Caucasian patients with late onset SLE. METHODS: Case records of 76 consecutive patients (age: 10-73 years) who attended the rheumatology clinic during the study period were reviewed. Chinese constituted 89.4% of the study population. RESULTS: Compared to the early onset patients, the late onset lupus patients tended to have an insidious onset of disease, lower female predominance and less frequent complaints of fever, alopecia, arthritis, and malar rash at presentation (p < 0.05). Peripheral neuropathy, myalgias, pancytopenia, and elevated liver enzymes were more commonly found in the late onset than in the early onset lupus during followup. Major organ involvement was relatively uncommon in late onset patients. No sex related differences could be demonstrated with respect to the mean age of onset of disease and clinical manifestations. No significant serological differences were detected between the 2 groups. The cause of death in the late onset group was often treatment related. CONCLUSION: Differences in disease manifestations were found between the early and late onset lupus patients. The disease expression in our predominantly Chinese elderly patients with lupus also differs from the Caucasian patients. However, the insidious onset and milder disease in the late onset group is in agreement with other studies.

Adolescent↗

Autoimmune thyroid disorders in SLE in Singapore.

One hundred and twenty-nine patients with systemic lupus erythematosus were screened for thyroid function tests. Of these, 8.9% had hyperthyroidism and 3.9% Hashimoto's thyroiditis. Euthyroid sick syndrome was present in 47.8% of patients. There was a high prevalence of antimicrosomal and antithyroglobulin antibodies (32.2%). Aberrations in thyroid function tests are common in SLE but the incidence of thyroid failure is low.

Adolescent↗

Infections in systemic lupus erythematosus.

A prospective study was carried out on the occurrence of infections in 28 hospitalised systemic lupus erythematosus (SLE) patients. In 38 episodes of infections, 23 were bacterial (60.5%), 4 were viral (10.6%) and culture negative infections were present in 10 (26.3%). The most common isolated organisms were Staphylococcus aureus (30.4%), Salmonella species (21.7%), Pseudomonas species (13.0%), and Klebsiella species (13.0%). The care rate was 94.7%. Death occurred in 2 patients. Lupus activity, impaired renal function, and cytotoxic therapy did not predispose to infection.

Adolescent↗

Ankylosing spondylitis in Singaporean Chinese--a clinical profile.

The clinical characteristics of 38 local Chinese ankylosing spondylitis patients were studied by interview, clinical examination and review of casenotes. The sex ratio was 3.2:1 in favour of males. The average duration from onset of symptoms till diagnosis of disease was 7.25 years. Peripheral joint involvement occurred in 71% of the patients. Extra-articular complications were uncommon; only three patients had a history of uveitis and one patient had biopsy proven IgA nephropathy. 26.3% of patients had significant disability due to the disease. Early diagnosis of the disease should be made as it may improve the prognosis of the patients.

Adult↗

Hepatitis B virus infection in patients with systemic lupus erythematosus.

Sera from 76 patients with systemic lupus erythematosus (SLE) were examined for HBsAg, anti-HBsAb and total anti-HBcAB by radioimmunoassay. Fifteen patients (19.7%) had one or more of these serological markers of HBV infection. This is comparable to the sero-prevalence in 100 sex- and age-matched healthy individuals (19%). There was no significant difference in the prevalence of HBV infection in patients who had received immunosuppressants compared with those who had not. Patients who had received transfusion of blood or blood products had a higher prevalence of serological markers but this was not statistically significant.

Adolescent↗

Open lung biopsy in systemic lupus erythematosus patients with pulmonary disease.

Open lung biopsy is an important diagnostic tool in immunocompromised patients with lung disease. This study evaluates the efficacy and safety of this procedure as part of the diagnostic work up in patients with Systemic Lupus Erythematosus (SLE) and lung disease. The casenotes of twelve SLE patients who had open lung biopsy were reviewed and the patients' clinical characteristics, laboratory investigations and outcome of the open lung biopsy were noted. Ten patients had bilateral reticulo-nodular opacities in the chest radiographic film while one had a persistent nodule in the right lower lobe and one had a normal chest X-ray. All the lung biopsy specimens had a diagnostic yield, e.g. interstitial pneumonitis, pneumonia, interstitial fibrosis and miliary tuberculosis. Three patients developed complications post-operatively, namely superimposed infection and pneumothorax. All responded to treatment. There were no deaths attributable to the surgical procedure. The high diagnostic yield and low morbidity in open lung biopsy support its use in the evaluation of pulmonary disease in SLE.

Adolescent↗

Anticardiolipin antibodies, haemolytic anaemia and thrombocytopenia in systemic lupus erythematosus.

Anticardiolipin antibody (ACA) levels were determined in 17 Asian female SLE patients with autoimmune haemolytic anaemia (AIHA) and 29 Asian female SLE inpatients without AIHA (control patients). Both IgG and IgM isotypes were measured by ELISA. Elevated IgM APA titres (greater than 5 SD of normal health controls) were seen in 11 (64.7%) of 17 AIHA patients and six (20.7%) of 29 control patients (P less than 0.01). There was no significant difference in IgG ACA titres between the two groups. Thrombocytopenia was present in 11 (64.7%) of the AIHA patients and nine (31%) of the control patients (P less than 0.05). None of the control SLE patients with thrombocytopenia had raised IgM ACA levels and only one had an elevated IgG ACA titre. Autoimmune haemolytic anaemia occurring in the context of SLE frequently associated with the concomitant presence of thrombocytopenia (Evan's syndrome) and with the presence of ACA.

Anemia, Hemolytic, Autoimmune↗

Polyneuropathy following intra-muscular sodium aurothiomalate for rheumatoid arthritis--a case report.

A patient with rheumatoid arthritis developed rapid onset of peripheral neuropathy whilst on treatment with intra-muscular (IM) gold (Sodium Aurothiomalate). At the time of admission, the arthritis was relatively quiescent. Electromyogram showed evidence of sensorimotor polyneuropathy. Investigations excluded other causes of polyneuropathy. Sural nerve biopsy did not reveal inflammation or vasculitis. The patient's condition improved after cessation of gold therapy. Gold induced neuropathy should be considered in a patient with rheumatoid arthritis who presents with polyneuropathy while on gold therapy.

Adult↗

Acute surgical abdomen in systemic lupus erythematosus--an analysis of 10 cases.

Gastrointestinal manifestations in a lupus patient may be due to different aetiologies such as vasculitis or a surgical condition. Problems of diagnosis are frequently encountered because the clinical presentations may mimic each other. We analysed ten lupus patients with acute surgical abdomen to identify the clinical, laboratory and radiological features that may aid in early diagnosis and management. Three patients with surgical abdomen had concomitant active lupus. Intra-abdominal sepsis and bleeding peptic ulcer disease constituted two major causes of laparotomies. Overt signs of peritonitis might not be present due to steroid masking effect. There were no specific clinical features, laboratory or radiological tests that could distinguish gastrointestinal vasculitis from acute surgical abdomen. Blood cultures, C-reactive protein and CT abdomen were useful adjuncts in the management of abdominal sepsis. No correlation was found between the timing of surgery, mortality, steroid dosage and wound complication.

Abdomen, Acute↗

The antiphospholipid syndrome.

The antiphospholipid syndrome (APS) describes an entity characterised by recurrent thrombosis, recurrent spontaneous abortions, thrombocytopenia, and elevated levels of antiphospholipid antibodies (IgG or IgM). The clinical features of APS include manifestations of thrombosis and/or cell damage. There is usually an associated underlying connective tissue disorder. The primary antiphospholipid syndrome refers to the presence of these clinical features without evidence of an associated autoimmune disorder. Detection of these antibodies include the lupus anticoagulant test, VDRL test and assays for anticardiolipin antibodies. Overlapping populations of these antibodies are detected by various immunologic tests. Management is based on the use of immunosuppressives, platelet inhibitors and anticoagulants.

Antiphospholipid Syndrome↗

HLA in Singapore Chinese with rheumatoid arthritis.

The HLA-A, B, C, DR and DQ antigens were determined in 50 Singapore Chinese patients with rheumatoid arthritis (RA). There was a significant increase in the prevalence of HLA-Bw46, DRw53 and DQ3 in patients with RA. The linkage disequilibrium between Bw46 and DRw53 explains this association. This major histocompatibility complex association differs from the HLA-DR4 link in Caucasian populations and suggests that RA is an immunogenetically heterogeneous disease.

Adult↗

Treatment strategies in rheumatoid arthritis.

Intervention therapies in rheumatoid arthritis (RA) are directed at the immune dysregulation and chronic inflammatory events in the joint. An ideal therapeutic program would rapidly control inflammation, prevent joint damage and preserve function. The various strategies of treatment involve the use of disease-modifying anti-rheumatic agents (DMARDs) either singly or in combination. Gold salts, penicillamine, sulphasalazine, methotrexate and hydroxychloroquine are used when NSAIDs fail to control inflammation. RA not only decreases the functional disability but the life-span of patients. The traditional pyramid strategy which uses single DMARDs consecutively has been found to be inadequate and slow in suppressing joint inflammation. Hence the race to find treatment regimes and strategies that will favourably alter the outcome of RA patients. Both the "step-down bridge" approach and saw-tooth strategy have been advocated in the attempt to break the progression of joint disease. None of the known regimes can be said to be most beneficial and least toxic.

Arthritis, Rheumatoid↗