Fatal cases of disseminated nocardiosis: challenges to physicians and clinical microbiologists - Case report.

Despite the development in the identification of Nocardia spp., common challenges exist in the laboratory diagnosis and management of nocardiosis. We report two cases of disseminated nocardiosis in a patient with hematologic disorder and in a patient with systemic lupus erythematosus, where the cooperation between various specialists was essential to set up the adequate diagnosis of disseminated nocardiosis.

Neuroimmune interactions in Sjögren's syndrome: relationship of exocrine gland dysfunction with autoantibodies to muscarinic acetylcholine receptor-3 and mental health status parameters.

OBJECTIVES: Antimuscarinic acetylcholine receptor-3 (m3AChR) autoantibodies have been described in primary Sjögren's syndrome (pSS). The aim of this study was to compare various methods for their detection and to assess the contributions of anti-m3AChR and other immunological and psychosocial factors to the pathomechanism of secondary SS (sSS). METHODS: Sixty-five rheumatoid arthritis (RA) patients, 103 systemic lupus erythematosus (SLE) patients, 76 pSS patients and 50 controls were compared. Three immunodominant epitopes of m3AChR were synthesized and used in ELISA. Two extracellular epitopes were also prepared in fusion with glutathione-S-transferase and one in conjugation with bovine serum albumin. Mental health status was assessed with the 36-item Short-Form Health Survey and Functional Assessment of Chronic Illness Therapy fatigue scale. Correlations were evaluated between glandular function and anti-m3AChR positivities and specificities, features of SLE and RA, and mental health parameters. RESULTS: Fourteen RA and 27 SLE patients had sSS. The autoantibody levels to all epitopes of m3AChR were significantly higher in pSS and SLE patients than in the controls. The fusion protein forms discriminated RA from pSS and SLE; furthermore, the YNIP fusion protein also distinguished pSS from SLE. The prevalence and the mean levels of all autoantibodies did not differ statistically between sicca and non-sicca SLE or RA patients. Glandular dysfunction correlated with higher age in SLE and RA and an impaired health-related quality of life in SLE. CONCLUSIONS: The second and third extracellular loops of m3AChR are antigenic in pSS. Immunoassays with antigens as fusion peptides demonstrate the best performance. Sicca SLE patients have worse mental health status. Anti-m3AChR antibodies represent a peculiar example of neuroimmune interactions.

Association between autoimmune pancreatitis and systemic autoimmune diseases.

AIM: To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4). METHODS: The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT). RESULTS: Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sjögren's syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto's thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level. CONCLUSION: The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.

A peptide of human muscarinic acetylcholine receptor 3 is antigenic in primary Sjogren's syndrome.

To evaluate the antigenicity of a peptide representing a part of the second extracellular loop of the human muscarinic acetylcholine receptor 3 (m3AChR) with autoimmune sera from primary Sjogren's syndrome (pSS), enzyme-linked immunosorbent assays (ELISAs) were developed. On the basis of the computer-predicted data, a 16-mer synthetic peptide KRTVPPGECFIQFLSE (KRSE213-228) was produced by solid-phase peptide synthesis. cDNA coding for the KRSE peptide was chemically synthetized and utilized to express the recombinant glutathione S-transferase (GST)-KRSE fusion protein. The immunoreactivities of the two antigens were tested in ELISAs with the sera of 40 pSS patients and 40 healthy controls. The specificity of the reaction was confirmed by inhibition assays and immunoblottings. The pSS sera resulted in significantly higher mean optical densities than those of the healthy controls (KRSE: 0.4149 vs 0.1494, p<0.0001; GST-KRSE 0.4765 vs 0.1764, p<0.0001). The immunological recognition with the recombinant fusion antigen was significantly better than that for the free peptide (p=0.0068). The sensitivities of the assays were 77.5% (KRSE) and 97% (GST-KRSE). The results of the concentration-dependent inhibition assays by the two systems of peptide presentation indicated that the KRSE sequence is specific for pSS sera. This is the first demonstration of the antigenicity of a novel peptide fragment of the human m3AChR in pSS. The analysed peptide could be of diagnostic relevance.

[The incidence of renal diseases as diagnosed by biopsy in Hungary]. / A biopsziával kórismézett vesebetegségek gyakorisága a Dél-Alföldön.

AIM AND METHODS: The authors analysed the incidence of renal diseases as diagnosed by biopsy in the population living on the southern Great Hungarian Plain. 798 biopsy specimens were examined between 1990 and 2002. RESULTS: The most common diseases in decreasing order of frequency were IgA nephropathy (15%), membranous nephropathy (12%), thin-basement-membrane nephropathy (8%), minimal change nephropathy (7%), lupus glomerulonephritis (7%), focal sclerosis (6%), hypertensive kidney disease and arteriolosclerosis (5%), diabetic nephropathy (5%), and crescentic glomerulonephritis (4%). The most frequent diseases in decreasing order of frequency in children were minimal change nephropathy, thin-basement-membrane nephropathy, Henoch-Schönlein nephropathy and IgA nephropathy; in adults were IgA nephropathy, membranous nephropathy, lupus glomerulonephritis and thin-basement-membrane nephropathy; and in the elderly were membranous nephropathy, amyloidosis, crescentic glomerulonephritis and diabetic nephropathy. The incidence of the diseases differed significantly between the genders in IgA nephropathy, thin-basement-membrane nephropathy, lupus glomerulonephritis, chronic sclerosing nephropathy and Alport nephropathy. At the time of the biopsy, 69 patients were suffering from diabetes mellitus. 37 patients were diagnosed as having diabetic nephropathy, and 32 as having non-diabetic nephropathy. In 6 cases, the diabetic nephropathy was accompanied by other glomerular disorders. In more than half of the diabetic patients with non-diabetic nephropathy, membranous nephropathy or focal sclerosis was diagnosed. Crescentic glomerulonephritis was diagnosed on 30 occasions, which was due to vasculitis in 20 cases, proliferative glomerulonephritis in 7 cases and anti-glomerular-basement-membrane nephritis in 3 cases. In the middle-aged and the elderly, the renal disease was relatively often a consequence of systemic disease. CONCLUSION: The incidence and the gender distribution of renal diseases diagnosed by biopsy were similar to those reported by other European kidney biopsy centres. IgA nephropathy was the most frequent disease in the biopsy registry of the authors. The high incidence of thin-basement-membrane nephropathy seems to be related to consequent biopsy examinations of glomerular haematuria. In diabetics and the elderly, the diagnosis of the renal disease may be challenging.

Cardiovascular autonomic dysfunction in primary Sjögren's syndrome.

OBJECTIVE: To assess the occurrence and clinical significance of a cardiovascular autonomic nervous system dysfunction in primary Sjögren's syndrome (pSS). METHODS: Fifty-one pSS patients participated in this case-control study. Heart rate and blood pressure variability measurements, spontaneous baroreflex sensitivity examinations and cardiovascular reflex tests were performed. RESULTS: The results of the heart rate and blood pressure variability measurements and also the baroreflex sensitivity parameters of the pSS patients peaked in the lowest percentile ranges of a database on 559 healthy control subjects (P < 0.05). In three of the five cardiovascular reflex tests, the frequencies of abnormal results were significantly higher among the patients than among the controls (P < 0.05), and the median autonomic neuropathy score was also elevated (3 vs 0 in the controls; P < 0.0001). CONCLUSION: Signs of an autonomic nervous system dysfunction involving the cardiovascular system can be discerned in the majority of pSS patients.