Association of beta2-Adrenergic Receptor Polymorphism with Work-Related Symptoms in Workers Exposed to Wheat Flour

PURPOSE: Our previous study indicated that the presence of wheat-specific IgG1 and IgG4 antibodies was associated with work-related symptoms in workers exposed to wheat flour. We performed this study to investigate the genetic polymorphisms of beta2-adrenergic receptors and wheat-specific antibodies in association with the clinical parameters of baker's asthma. MATERIALS AND METHODS: In total, 379 subjects working in a single industrial bakery were enrolled in this study. The skin prick test was performed with common inhalant allergens and wheat flour extract. The presence of serum- specific IgE, IgG1, and IgG4 antibodies to wheat flour were determined by ELISA. Whole blood samples were obtained for genotype analysis. Subjects were genotyped with regard to five candidate single nucleotide polymorphisms (SNPs) of the beta2-adrenergic receptor gene (ADRB2; -47 T>C, 46 A>G, 79 C>G, 252 G>A, and 523 C>A) using a single-base extension method. RESULTS: No significant associations were observed between the genotype/allele frequencies of any of the SNPs tested and any clinical parameters. The haplotype of ADRB2 (GAA composed of 46 A>G, 252 G>A, and 523 C>A) was significantly associated with work-related symptoms (pG and haplotype [GAA] of ADRB2, the prevalence rates of wheat-specific IgG1 antibodies and lower respiratory symptoms increased significantly with exposure intensity (both p<0.05). CONCLUSION: The findings of the present study suggest that ADRB2 genetic polymorphism may contribute to the development of work-related symptoms in workers exposed to wheat flour, which can lead to baker's asthma.

Clinical and Radiographic Features of Adult-onset Ankylosing Spondylitis in Korean Patients: Comparisons between Males and Females

The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4+/-8.9 yr and average disease duration was 9.6+/-6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober's test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment.

Immunoglobulin G Subclass Deficiency is the Major Phenotype of Primary Immunodeficiency in a Korean Adult Cohort

Primary immunodeficiency disease (PID) is a rare disorder in adults. Most often, serious forms are detected during infancy or childhood. However, mild forms of PID may not be diagnosed until later in life, and some types of humoral immunodeficiency may occur in adulthood. The purpose of this study was to identify clinical features of PID in Korean adults. A retrospective study was performed on 55 adult patients who were diagnosed as PID between January 1998 and January 2009 at a single tertiary medical center in Korea. IgG subclass deficiency was the most common phenotype (67%, 37/55), followed by total IgG deficiency (20%, 11/55), IgM deficiency (7%, 4/55), common variable immunodeficiency (2%, 1/55), and X-linked agammaglobulinemia (2%, 1/55). IgG3 and IgG4 were the most affected subclasses. Upper and lower respiratory tract infections (76%) were the most frequently observed symptoms, followed by multiple site infection (11%), urinary tract infection, and colitis. Bronchial asthma, rhinitis, and several autoimmune diseases were common associated diseases. IgG and IgG subclass deficiency should be considered in adult patients presenting with recurrent upper and lower respiratory infections, particularly in those with respiratory allergies or autoimmune diseases.

An Antinuclear Antibody-Negative Patient With Lupus Nephritis

Systemic lupus erythematosus (SLE) is a typical autoimmune disease that's characterized by various autoantibodies to nuclear and cytoplasmic antigens. The presence of antinuclear antibodies (ANA) in serum is generally considered a decisive diagnostic sign of SLE. However, a small subset of SLE patients who had the typical clinical features of SLE was reported to show persistently negative ANA tests. Our report describes a 16-yr-old female who presented with the clinical manifestations of SLE such as malar rash, photosensitivity, arthritis, lymphopenia, pericarditis and proteinuria. The serum autoantibodies were all negative and renal biopsy showed that the histopathological changes of immune complex mediated the focal segmental necrotizing glomerulonephritis with crescent formation. She was treated with monthly pulse cyclophosphamide along with corticosteroids. During the 2-yr follow-up period, the proteinuria was markedly decreased and all of the ANA and anti-double stranded DNA antibody tests were negative. This case suggests that ANA may not be required in the pathogenesis of lupus nephritis.

Identification of Dioscorea Batatas (Sanyak) Allergen as an Inhalant and Oral Allergen

Dioscorea batatas is widely used in Asia as a herbal medicine or food product with potential health benefits. There have been several reports of occupational asthma caused by inhalation of D. batatas dust. However, there has been no report of systemic allergic reactions after oral administration of D. batatas. Two patients with D. batatas allergy were enrolled. One had experienced severe urticaria and angioedema after indigestion, and the other had been exposed to D. batatas dust and was diagnosed as having occupational asthma. Both patients had high serum-specific IgE and IgG4 antibodies to D. batatas. And IgE immunoblot demonstrated that both sera bound to a 27-kDa protein with an IgE-binding motif, which was revealed by 2-D-electrophoresis to have the sequence Asn-Val-Glu-Asp-Glu-Phe-Ser-X-Ile- Glu-Gly-Asn-Pro-X-X-Pro-Glu-Asn-X-Gly (pI 6.40, 6.04). In conclusion, discorin from D. batatas (DB3S) was identified as the major allergen of D. batatas in patients sensitized via an oral or inhalant route.

Association of Specific IgE to Staphylococcal Superantigens with the Phenotype of Chronic Urticaria

It has been well established that bacterial superantigens lead to the induction and aggravation of chronic inflammatory skin diseases. We investigated the clinical significance of serum specific immunoglobulin E (lgE) to the staphylococcal superantigens staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB), and toxic shock syndrome toxin (TSST)-1 in patients with chronic urticaria (CU), focusing on the differences in these prevalences between aspirin-intolerant CU (AICU) and aspirin-tolerant CU (ATCU) patients. Aspirin sensitivity was confirmed by oral aspirin provocation test. There were 66 patients AICU and 117 patients ATCU in the study. Serum IgE antibodies specific for SEA, SEB, and TSST-1 were measured by the ImmunoCAP test and the patients were compared with 93 normal controls (NC). The prevalences of serum specific IgE to staphylococcal superantigens were significantly higher in CU than in NC patients (IgE to SEA, 13.7% vs. 5.4%; IgE to SEB, 12.0% vs. 4.3%; IgE to TSST-1, 18.0% vs. 6.5%; p<0.05, respectively). The patients with specific IgE to SEA, SEB, and TSST-1 had higher serum total IgE levels and higher rates of atopy. Significant associations were noted between the prevalence of specific IgE to SEA and SEB and the HLA DQB1*0609 and DRB1*1302 alleles in the AICU group. We confirmed that a sub-population of patients with CU possesses serum IgE antibodies to SEA, SEB, and TSST- 1. Particularly, the IgE immune response to TSST-1 is associated with aspirin sensitivity in CU patients.

A Case of Late onset Peripheral Spondyloarthropathy / 대한류마티스학회지

The spondyloarthropathies are a group of inflammatory rheumatic diseases including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthropathy. It usually begins in young or middle aged adults, but sometimes presents with atypical symptoms in the older patients. Late onset spondyloarthropathies are characterized by severe disease, marked elevation of laboratory parameters of inflammation, oligoarthritis involving the lower limbs with edema of the extremities. We described a 66-year-old patient who presented with asymmetric polyarthritis mainly involving lower extremities with fever, marked elevation of laboratory inflammatory markers, and was successfully treated with mini-pulse corticosteroids with disease modifying antirheumatic drugs.

A Case of Rat Bite Fever Arthritis / 대한류마티스학회지

Rat bite fever is a rare, systemic illness caused by Streptobacillus moniliformis or Spirillum minus following a rat or other rodent bite. Characteristically, fever develops abruptly with maculopapular skin rash after an incubation period of two to ten days, and asymmetric migrating polyarthritis starts later in up to 50% of patients. The arthritis involves the knees, shoulders, elbows, wrists and hands, which may either be suppurative or non-suppurative. Although most cases seem to resolve spontaneously within two weeks, the mortality in untreated cases is around 10~15%. The response to antibiotic treatment is good and early diagnosis is the most important prognostic factor. We report a patient who developed arthritis with fever after biting by rat.

A Case of Polymyositis Associated with Primary Biliary Cirrhosis / 대한류마티스학회지

The coexistence of polymyositis and primary biliary cirrhosis is rare. Both are characterized by chronic inflammation and immunological abnormalities. We report a case of 54-year-old female patient presenting with these two autoimmune diseases. She exhibited symmetrical proximal muscle weakness and elevated serum levels of muscle enzymes. Polymyositis was confirmed by electromyography and muscle biopsy. The diagnosis of primary biliary cirrhosis was based on increased serum levels of alkaline phosphatase, IgM immunoglobulin, presence of antimitochodrial antibody and characteristic liver biopy findings. This is the first case who manifest polymyositis and primary biliary cirrhosis simultaneously in Korea.

A usefulness of urinary K/Cr ratio as differential diagnosis of acute hypokalemic paralysis / 대한내과학회지

BACKGROUND: Acute hypokalemic paralysis, a clinical syndrome characterized by acute systemic weakness and low serum potassium, is a rare but treatable cause of acute weakness. The aim of our study is to analyze the cause of hypokalemic paralysis and to define clinical characteristics of hypokalemic paralysis. METHODS: Hypokalemia was defined as a serum potassium concentration less than 3.0 mEq/L in this study. A total 31 patients with hypokalemic paralysis (male 71%, mean age; 35.7 +/- 14.3 years) have been studied retrospectively from June 1994 to March 2004 for the evaluation of clinical characteristics. According to the pathophysiology of hypokalemia, patients were divided into the potassium renal loss group (n=9) and the potassium shift group (n=14). We calculate the UK/UCr (mmol/mmol) ratio, Transtubular K+ concentration gradient (TTKG) and compared the results between two groups. RESULTS: The cause of hypokalemic paralysis was hyperthyroidism (45.2%), medication (19.4%), renal disease (6.5%), hyperaldosteronism (3.2%), poor oral intake (3.2%), vomiting (3.2%), and unknown origin (19.4%). There was a significant difference of UK/UCr ratio (p=0.046) but no significant difference of TTKG (p=0.116) between the potassium loss and shift groups. CONCLUSION: The most common cause of acute hypokalemic paralysis is hyperthyroidism. The UK/UCr ratio is more useful measure than TTKG in differentiation of potassium loss and potassium shift as a cause of hypokalemia.

Quantitative Viral Load Monitoring and Cidofovir Therapy in BK Virus Nephropathy / 대한신장학회잡지

BACKGROUND: BK virus nephropathy (BKVN) has been increasingly recognized as an important cause of renal transplant dysfunction, but no specific antiviral therapy is currently available. Furthermore, a method evaluating the degree of viral infection has not been developed yet. Recently, there have been several case reports in which BKVN was successfully treated with cidofovir injection. In the current study, we report a case with BKVN successfully treated with cidofovir injection. In addition, we assessed the usefulness of quantitative viral load monitoring using a competitive polymerase chain reaction (PCR) in the treatment of BKVN. METHODS: A renal allograft recipient with BKVN was injected with cidofovir. To monitor BK viral load in urine and plasma, we developed a competitive PCR assay and followed the patient prospectively. RESULTS: A 49 year old renal transplant recipient developed a progressive rise in serum creatinine reaching 1.9 mg/dL at 15 months post-transplantation. Subsequently, the patient was diagnosed as BKVAN by allograft biopsy. At this time, BKV DNA was detected in plasma and urine. Despite a reduction of the dose of mycophenolate mofetil, serum creatinine continued to rise, which prompted the initiation of cidofovir trial. The patient was given intravenous cidofovir. After cidofovir treatment, BK virus associated findings disappeared on repeat biopsy, and BK virus in plasma was decreased to the undetectable level. For 7 months after cidofovir treatment, her renal function remained stable. CONCLUSION: Cidofovir therapy may be effective in the treatment for BKVN. Viral load in plasma reflected well the clinical and pathological course of the BK virus infection.