To understand the clinical significance and mechanisms of cutaneous denervation in systemic lupus erythematosus (SLE), we assessed intraepidermal nerve fibre (IENF) density of the distal leg in 45 SLE patients (4 males and 41 females, aged 38.4 +/- 13.6 years) and analysed its correlations with pathology, lupus activity, sensory thresholds and electrophysiological parameters. Compared with age- and gender-matched control subjects, SLE patients had lower IENF densities (3.08 +/- 2.17 versus 11.27 +/- 3.96 fibres/mm, P < 0.0001); IENF densities were reduced in 38 patients (82.2%). Pathologically, 11 patients (24.4%) were found to have definite cutaneous vasculitis; the severity and extent of cutaneous vasculitis were correlated with IENF densities. Patients with active lupus had even lower IENF densities than those with quiescent lupus (1.86 +/- 1.37 versus 4.15 +/- 2.20 fibres/mm, P = 0.0002). By linear regression analysis, IENF densities were negatively correlated with the SLE disease activity index (r = 0.527, P = 0.0002) and cumulative episodes of lupus flare-up within 2 years before the skin biopsy (r = 0.616, P = 0.0014). Clinically, skin denervation was present not only in the patients with sensory neuropathy but also in the patients with neuropsychiatric syndrome involving the CNS. SLE patients had significantly elevated warm threshold temperatures (P = 0.003) and reduced cold threshold temperatures (P = 0.048); elevated warm threshold temperatures were associated with the reduced IENF densities (P = 0.032). In conclusion, cutaneous vasculitis and lupus activities underlie skin denervation with associated elevation of thermal thresholds as a major manifestation of sensory nerve injury in SLE.
The results of this study suggest that therapy with 5 mg pilocarpine four times daily is effective, safe and well tolerated for the relief of oral symptoms in patients with SS in Taiwan.
BackgroundPen c 13, identified as a 33-kDa alkaline serine protease, is a major allergen secreted by Penicillium citrinum. Detailed knowledge about the epitopes responsible for IgE binding would help inform the diagnosis/prognosis of fungal allergy and facilitate the rational design of hypoallergenic candidate vaccines. The goal of the present study was to characterize the IgE epitopes of Pen c 13.Methodology/Principal FindingsSerum samples were collected from 10 patients with mold allergy and positive Pen c 13 skin test results. IgE-binding epitopes on rPen c 13 were mapped using an enzymatic digestion and chemical cleavage method, followed by dot-blotting and mass spectrometry. A B-cell epitope-predicting server and molecular modeling were used to predict the residues most likely involved in IgE binding. Theoretically predicted IgE-binding regions were further confirmed by site-directed mutagenesis assays. At least twelve different IgE-binding epitopes located throughout Pen c 13 were identified. Of these, peptides S16 (A148–E166) and S22 (A243–K274) were recognized by sera from 90% and 100% of the patients tested, and were further confirmed by inhibition assays. Peptide S22 was selected for further analysis of IgE-binding ability. The results of serum screening showed that the majority of IgE-binding ability resided in the C-terminus. One Pen c 13 mutant, G270A (T261–K274), exhibited clearly enhanced IgE reactivity, whereas another, K274A, exhibited dramatically reduced IgE reactivity.Conclusions/SignificanceExperimental analyses confirmed in silico-predicted residues involved in an important antigenic region of Pen c 13. The G270A mutant of Pen c 13 has the potential to serve as an additional tool for the diagnosis/prognosis of mold allergy, and the K274A mutant, as a hypoallergenic form of the epitope, may provide a framework for the design and development of a safe and efficient therapeutic strategy for treating human allergic diseases.
Lupus cystitis was rare but frequently resulted in obstructive uropathy and had a strong association with gastrointestinal (GI) symptoms. We treated six patients with systemic lupus erythematosus (SLE) and obstructive uropathy from January 1996 to December 2001 in a university hospital. Evidence of cystitis was obtained from cystoscopic biopsy or the presence of thickened bladder wall in image study. Similar to other reports, five patients had GI manifestations such as abdominal pain, nausea/vomiting, diarrhoea or ileus. In addition, mesenteric lymphadenopathy or pancreatitis was noted in three patients. Two patients had been treated for idiopathic thrombocytopenic purpura (ITP), four and 20 years ago, respectively. All six patients had antibodies to double-stranded DNA (dsDNA). Five patients each had antibodies to cardiolipin (IgG aCL) or SSA. The high prevalence of anti-SSA had also been reported in Chinese lupus patients with intestinal pseudo-obstruction, a clinical manifestation frequently associated with bilateral ureterohydronephrosis. Two patients died of intractable infection after the surgical procedures for persistent ureterohydronephrosis and both patients had antibodies to ribosomal P proteins. Lupus cystitis might not be so rare in Chinese patients with SLE. The diagnosis should be kept in mind when lupus patients have urinary and/or GI symptoms.
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