Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 11681500 | Measuring the lacunar sulci as a new indicator of shrinkage of the ocular surface. | 2001 Jul | PURPOSE: To present a new indicator that measures the sulci of the lacrimal lake of the eye according to the degrees of ocular abduction at which they vanish. This new approach will help determine the severity and progression of mucosal retraction in ocular surface diseases. METHODS: A total of 181 eyes of 94 healthy persons, 130 eyes of 65 patients with Sjogren's syndrome, and 30 eyes of 15 patients with ocular pemphigoid were examined using the slit lamp. We recorded the vanishing point of the three main lacunar sulci (plico-bulbar, plicocaruncular and dermo-caruncular) while abducting. RESULTS: In healthy persons, the average vanishing points for the first and second lacunar sulci were respectively, 53.20 +/- 12.3 and 54.50 +/- 9.8. In patients with Sjogren's syndrome, 49.53 degrees +/- 10.81 and 53.17 degrees +/- 7.28 and in patients with incipient ocular cicatricial pemphigoid, 42.69 degrees +/- 14.33 and 44.46 degrees +/- 16.85. Statistical significance was p < 0.005. CONCLUSIONS: The lacunar sulci are shallower and vanish sooner in ocular cicatricial pemphigoid and Sjogren syndrome than in normals. Investigating the vanishing point of the lacunar sulci while abducting is useful for grading the shrinkage of the conjunctiva, caruncle and medial canthus. | |
| 9256612 | [A refractory case of adult-onset Still's disease]. | 1997 Jun | We report here a case of adult-onset Still's disease (AOSD), who finally responded to a combination of cyclophosphamide (CPA) and gold sodium thiomalate (GST) after two years of active disease. A 23-year-old man having continuous high fever with skin rash, polyarthralgia and increased serum ferritin, was diagnosed as AOSD, and oral corticosteroid was initially effective. His symptoms recurred one year later without clinical improvement to increased dosage of steroid. He was admitted to our hospital with pericarditis and pleural effusion but did not respond to either intravenous (i.v.) pulse steroid therapy, methotrexate (MTX) or high dose i.v. gamma-globulin. He was partly responsive to monthly i.v. injection of CPA, but clinical symptoms did not completely subside and hyperferritinemia persisted. GST, initiated in combination with CPA, however, was successful to induce complete remission. MTX has recently been reported to be efficacious to steroid-resistant AOSD, but CPA and gold compounds might be useful to refractory case of AOSD. | |
| 10640777 | Viral IL-10 and soluble TNF receptor act synergistically to inhibit collagen-induced arthr | 2000 Feb 1 | Viral IL-10 (vIL-10) and soluble TNF receptor (sTNFR) are anti-inflammatory proteins that can suppress collagen-induced arthritis (CIA). These and related proteins have shown efficacy in the treatment of human rheumatoid arthritis; however, neither alone is able to completely suppress disease. Furthermore, they have short half-lives, necessitating frequent administration. To determine the ability of these proteins to act synergistically following gene transfer, arthritis was induced in DBA/1 male mice by immunization with type II collagen on days 0 and 21. Mice were injected i.v. either before disease onset (day 20) or after disease onset (day 28) with 1010 particles of adenovirus encoding vIL-10, a soluble TNF receptor-IgG1 fusion protein (sTNFR-Ig), a combination of both vectors, or a control vector lacking a transgene. Significant synergism was observed with the combination of vIL-10 and sTNFR-Ig, with a substantial reduction in both the incidence and severity of disease as well as inhibition of progression of established disease. sTNFR-Ig alone had no effect on CIA. vIL-10 alone inhibited disease when given before disease onset, but had minimal effect on established disease. Both proteins inhibited spleen cell proliferation and IFN-gamma secretion in response to stimulation with type II collagen, but only vIL-10 reduced the synovial mRNA levels of the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6. These findings demonstrate that vIL-10 and sTNFR-Ig act synergistically in suppressing CIA and suggest that gene transfer offers a potential therapeutic modality for the treatment of arthritis. | |
| 9566349 | Natural anti-immunoglobulin autoantibodies: irrelevant by-products or immunoregulatory mol | 1998 Apr | Anti-immunoglobulin autoantibodies (anti-Ig auto-Abs), particularly IgM-anti-IgG (classical rheumatoid factor), have been studied mainly in the context of rheumatoid arthritis. In this article we focus on other members of the anti-Ig family, including the natural IgG-anti-F(ab')2 auto-Ab, and look for clinical and experimental findings supporting a role of these antibodies in the regulation of the immune response. We discuss the evidence for suppression of auto- and alloreactive B cells by IgG-anti-F(ab')2 auto-Ab and the role of this Ab in the pathogenesis of certain diseases, such as autoimmune hemolytic anemia. The structure of the antibody's antigen-binding site was clarified by isolating the VL and VH gene segments from the cDNA of B cells. Sequence analyses revealed germline gene identity of VL chains and 88% homology with the closest germline gene of VH chains. Finally, we discuss hypothetical models concerning the immunoregulatory role of natural anti-Ig auto-Abs. | |
| 10687410 | [RS3PE syndrome or benign edematous polysynovitis in the elderly. Study of 8 cases]. | 1999 Dec | BACKGROUND: The RS3PE syndrome is a recently described uncommon disorder in the elderly patient; in the initial reports, it was characterized by an excellent prognosis with total remission. In contrast with rheumatoid arthritis and polymyalgia rheumatic, it has been related to HLA B7. Further works have questioned its benign nature and even that it is a new entity. Our objective was to study the clinico-biological characteristics, therapy, and clinical course in patients with RS3PE attended at our clinic. METHODS: Retrospective descriptional study of patients with RS3PE attended in our clinic from January 1992 to December 1998 following the inclusion criteria proposed by Olivé et al. For all patients, the following determinations and studies were performed: complete blood count, ESR, serum biochemistry, two measurements of rheumatoid factor (RF), and X-ray. Class I HLA typing was determined in five cases. RESULTS: Eight patients were found (6 men and 2 women), with a mean age of 68.7 years. The arthritis was more common at MCP, wrists, shoulder, and PIF in hands. Four patients had tenosynovitis of the hand flexors. ESR (mean: 69.3) and RCP (mean: 49.7) were increased in most cases. Seven patients had leukocytosis. HLA B7 was positive for 4 out of five patients. All patients were treated with low-dose corticosteroids, with a mean length of 9.5 months. Three patients had relapses. During follow-up after therapy had been completed, none of the patients had other diseases. CONCLUSIONS: RS3PE syndrome involves elderly patients and its clinical course is characterized by sudden onset seronegative symmetrical polysynovitis, with pitting edema over the hand dorsum and less commonly over the pretibial region. In most cases, a marked acute-phase reaction and leukocytosis were observed. Therapy with low-dose corticosteroids is effective; sometimes however, it is necessary to add antimalarial agents. The three patients who relapsed had underlying diseases: chronic lymphocytic leukemia, Sjögren's syndrome, and liver cirrhosis, respectively. The diagnosis of RS3PE should be obtained a posteriori, after a prolonged follow-up of the patient. Atypical cases, with evolution towards other rheumatic or hematological disorders or as paraneoplastic manifestation, have been reported. | |
| 24383561 | Participation of substance P distribution in the cytokine production of rheumatoid synoviu | 2000 Jun | Abstract Based on findings which suggested the involvement of the neuropeptide substance P in the pathogenesis of rheumatoid arthritis (RA), we investigated the mechanism of synovial pannus formation in RA, and examined the interaction between the cytokine production of synovial tissues and the concentration of substance P in the cartilage-pannus junction (CPJ). The CPJ and other peripheral synovial tissues were separately obtained from each part of the synovium from the knee joints of seven RA patients. The concentrations of substance P and the cytokines interleukin (IL)-1β and IL-6 in the CPJ and peripheral synovial tissues were determined by enzyme-linked immunosorbent assays. In addition, synovial cells were isolated from the CPJ and peripheral synovial tissues and treated with substance P or neurokinin-1 receptor antagonist to analyze the changes in cytokine production. The substance P levels were 211.2 and 50.5 pg/mg protein in the CPJ and the peripheral synovium, respectively. The IL-1β and IL-6 levels in the CPJ were 24.6 and 12.8 pg/mg protein, respectively. In the peripheral synovium, these levels were 4.3 and 2.5 pg/mg protein, respectively. In the CPJ, the IL-1β and IL-6 levels in tissue containing a high concentration of substance P (>200 pg/mg protein) were 39.4 and 21.6 pg/mg protein, respectively, and those in tissue containing a low concentration of substance P (≤200 pg/mg protein) were 11.6 and 5.1 pg/mg protein, respectively. Synovial cells from the CPJ produced higher levels of IL-1β and IL-6 than those from peripheral tissues. In addition, treatment of the cells with an NK-1 antagonist significantly reduced the production of these cytokines by the synovial cells. The theory that substance P plays a role in the pathogenesis of RA via the upregulation of cytokine production should be considered in further studies on the immunomodulatory properties of substance P in arthritis. | |
| 9641270 | Nitric oxide in arthritis. | 1998 Jun | Nitric oxide's (NO) involvement in arthritis was first demonstrated when levels of nitrite, a stable endproduct of NO metabolism, were shown to be elevated in serum and synovial fluid samples of rheumatoid and osteoarthritis patients. NO production by chondrocytes, its involvement in various biochemical events of cartilage metabolism, and the in vivo suppression of experimental arthritis by NO synthase inhibitors further implicated NO in arthritis. However, a conclusive role for NO in the pathogenesis of arthritis remains to be defined, in contrast to the NO-cGMP signal transduction pathway of endothelium-mediated vasodilation. It appears that NO has limited modulating effects in cartilage metabolism, with evidence for both protective and deleterious effects. Recent developments that contribute to our understanding of NO's role in arthritis are discussed. | |
| 10047723 | [A case of psoriatic arthritis associated with ankylosing spondylitis treated with bilater | 1998 Dec | We report a case of a 40-year-old male with psoriatic arthritis associated with ankylosing spondylitis. At the age of 34, the patient suffered pain in his hips, knees, ankles, neck and low back 3 years after the onset of psoriasis vulgaris. The hip pain gradually became severe despite the medical treatment and physical therapy. On admission, the skin lesion of diffuse erythematous plaques with scales was observed on the trunk and extremities. Motion of the spine was markedly limited. We also noted limitation of motion in the bilateral hips and remarkable gait disturbance. In laboratory findings, rheumatoid factor and HLA-B 27 antigen were negative. Radiographs of the cervical spine showed typical bamboo spine as seen in ankylosing spondylitis. Obliteration of the sacroiliac joints and joint space narrowing in the hips with reactive sclerosis were revealed on the pelvic film. Bilateral cementless total hip arthroplasty with adductor tenotomy resulted in complete pain relief and a marked improvement in gait function 18 months after surgery. The appropriate reconstructive surgery was extremely helpful to increase daily activities of the patient in this case. | |
| 9082942 | Adjuvant arthritis as a model of inflammatory cachexia. | 1997 Mar | OBJECTIVE: To determine whether adjuvant arthritis (AA) leads to changes in body composition and cytokine production similar to those seen in patients with rheumatoid arthritis. METHODS: AA was induced in Lewis rats using Freund's complete adjuvant. Body cell mass was measured by determining the concentration of total exchangeable potassium using 42K gavage. Splenocyte production of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) was measured by bioassay. Weight and food intake were also measured. RESULTS: Animals that developed AA lost 6% of their body weight by the onset of clinically evident arthritis (day 14; P < 0.01) and lost 20% by the end of the inflammatory phase of AA (day 28; P < 0.0001). Body cell mass fell 24.7 +/- 8.6% (mean +/- SEM) in animals with AA, but did not change significantly in controls (increase of 6.3 +/- 7.9%) (P < 0.03). Pair-fed animals lost one-fourth of the weight lost by the animals with AA (P < 0.01), indicating that anorexia alone does not explain inflammatory cachexia. Weight loss was correlated with TNF alpha production by spleen mononuclear cells (r = 0.68, P < 0.007), and a weaker correlation was seen with IL-1 production (r = 0.45, P < 0.04). CONCLUSION: AA in rats is a useful model of inflammatory cachexia that mimics the human pathophysiology in important ways, and is consistent with cytokine-driven cachexia in chronic inflammatory arthritis. | |
| 11145704 | IL-4 adenoviral gene therapy reduces inflammation, proinflammatory cytokines, vascularizat | 2001 Jan 15 | IL-4 is a cytokine with anti-inflammatory properties on activated macrophages. Rheumatoid arthritis, an autoimmune inflammatory disease, is characterized by a paucity of IL-4 and an abundance of synovial macrophage-derived mediators. Herein, the effect of a single injection of adenovirus-producing rat IL-4 (AxCAIL-4) or a control virus with no inserted gene was compared with the effect of PBS injection into rat ankles. Ankles were injected before arthritis onset or at maximal inflammation. Preventatively, AxCAIL-4 reduced adjuvant-induced arthritis (AIA)- and/or AIA/adenoviral-induced ankle inflammation, decreasing articular index scores, ankle circumferences, paw volumes, radiographic scores, mean levels of monocyte chemoattractant protein-1, the number of inflammatory cells, and the number of synovial blood vessels. Therapeutically, AxCAIL-4 also decreased ankle circumferences and paw volumes in comparison with a control virus with no inserted gene and PBS groups. After arthritis onset, mean levels of TNF-alpha, IL-1beta, macrophage inflammatory protein-2, and RANTES were decreased in AxCAIL-4 rat ankle homogenates compared with PBS-treated homogenates. Thus, increased expression of IL-4 via gene therapy administered in a preventative and/or therapeutic manner reduced joint inflammation, synovial cellularity, levels of proinflammatory cytokines, vascularization, and bony destruction in rat AIA, suggesting that a similar treatment in humans may be beneficial. | |
| 9212993 | Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, inhibits the development | 1997 Jun | We evaluated the effects of Z-100, extracted from human type Mycobacterium tuberculosis strain Aoyama B, on collagen-induced arthritis (CIA) in mice. One hundred thirty-five DBA/1J mice, 8 weeks of age, were assigned to 9 groups and immunized with bovine type II collagen (CII) or CFA. From the next day, Z-100 at doses of 0.004, 0.04, or 0.4 mg/kg B.W./d for 48 d was intradermally injected into the tail base. Methotrexate (MTX) at daily doses of 0.1, 0.3, or 1.0 mg/kg B.W. and cyclophosphamide (CY) at a daily dose of 5 mg/kg B.W. were used as reference drugs. The effects of these drugs on CIA mice were evaluated in terms of the incidence of CIA, the arthritis index (AI), and hind paw edema, after which the animals were sacrificed at 49 d, and both anti-CII antibody titer and delayed-type hypersensitivity (DTH) reaction were measured. In the arthritic control groups, the AI and hind paw edema were significantly increased after the second immunization on day 28. The anti-CII antibody titer and DTH reaction were significantly increased compared to normal mice on day 49. Z-100 significantly inhibited the AI at a dose of 0.4 mg/kg/d on day 49, and suppressed the incidence of both CIA and hind paw edema. Increases in both anti-CII antibody titer and DTH reaction in CIA mice were prevented by treatment with Z-100 at 0.4 mg/kg/d. MTX, in a dose-dependent manner, and CY, at a dose of 5 mg/kg/d, inhibited the incidence of CIA, AI, hind paw edema, anti-CII antibody titer and DTH reaction in CIA mice. Z-100 at a dose of 0.4 mg/kg was as effective as MTX was at a dose of 0.3 mg/kg against the DTH reaction, and it had no side effects. These results suggest the usefulness of Z-100 in patients with chronic rheumatoid arthritis. | |
| 10623444 | Production of interleukin (IL)-1beta, IL-1 receptor antagonist and IL-10 by blood mononucl | 2000 Jan | Joint erosion is a prevalent feature of rheumatoid arthritis (RA) but not of many other chronic inflammatory arthritides (non-RA). Joint destruction is mediated by cytokines, primarily interleukin (IL)-1 and tumour necrosis factor. Less erosive activity in patients with non-RA compared to RA might be related to factors that inhibit production and/or function of IL-1. Release of IL-1beta, and the two antagonists, IL-1 receptor antagonist (IL-1ra) and IL-10 from blood mononuclear cells were therefore quantitated by ELISA in 22 patients with RA, 11 with non-RA and 15 healthy age-matched controls. Release of IL-1beta was comparable between the three groups but only detectable in cultures stimulated with lipopolysaccharide; it decreased in patients treated with prednisolone: 3.8 ng/10(6)monocytes (median) vs 11.7 (P=0.045). Release of IL-1ra was in all but IgG-stimulated cultures comparable between groups. The ratio of IL-1ra/IL-1beta was elevated in LPS-stimulated cells from RA patients only: 2.0 versus 1.3 (P=0.02). In contrast, IgG-induced IL-1ra release was significantly elevated only in non-RA patients: 95 ng/10(6)monocytes vs 40 (P=0.014), and the levels correlated positively to those of blood CRP (P=0.02). Though stimulated release of IL-10 was similar between the three groups, the levels were lower in non-erosive than erosive arthritis patients, and controls (P=0. 05). In conclusion, increased IgG-stimulated IL-1ra release and elevated IL-1ra/IL-1beta ratio may protect against actions of IL-1 in vivo, and decreased release of IL-10 might be related to features of non-erosive arthritis. | |
| 11748266 | Therapeutic effect of neutralizing endogenous IL-18 activity in the collagen-induced model | 2001 Dec | Two distinct IL-18 neutralizing strategies, i.e. a rabbit polyclonal anti-mouse IL-18 IgG and a recombinant human IL-18 binding protein (rhIL-18BP), were used to treat collagen-induced-arthritic DBA/1 mice after clinical onset of disease. The therapeutic efficacy of neutralizing endogenous IL-18 was assessed using different pathological parameters of disease progression. The clinical severity in mice undergoing collagen-induced arthritis was significantly reduced after treatment with both IL-18 neutralizing agents compared to placebo treated mice. Attenuation of the disease was associated with reduced cartilage erosion evident on histology. The decreased cartilage degradation was further documented by a significant reduction in the levels of circulating cartilage oligomeric matrix protein (an indicator of cartilage turnover). Both strategies efficiently slowed disease progression, but only anti-IL-18 IgG treatment significantly decreased an established synovitis. Serum levels of IL-6 were significantly reduced with both neutralizing strategies. In vitro, neutralizing IL-18 resulted in a significant inhibition of TNF-alpha, IL-6, and IFN-gamma secretion by macrophages. These results demonstrate that neutralizing endogenous IL-18 is therapeutically efficacious in the murine model of collagen-induced arthritis. IL-18 neutralizing antibody or rhIL-18BP could therefore represent new disease-modifying anti-rheumatic drugs that warrant testing in clinical trials in patients with rheumatoid arthritis. | |
| 10914840 | Suppression of collagen induced arthritis in mice utilizing plasmid DNA encoding interleuk | 2000 Jul | OBJECTIVE: To investigate the therapeutic efficacy as well as the immunological effects of inoculation of an expression vector encoding interleukin 10 (IL-10) in murine type II collagen induced arthritis (CIA). METHODS: CIA was induced in DBA/1 Lac/J mice by immunization with bovine type II collagen (CII) in Freund's complete adjuvant (FCA), followed by immunization of CII in Freund's incomplete adjuvant (FIA) 3 weeks later (CIA mice). The plasmid cytomegalovirus (pCMV) vector encoding IL-10 (pCMV-IL-10) was inoculated intradermally into DBA/1 Lac/J mice (pCMV-IL-10 CIA mice) one week prior to first immunization with CII. CIA mice inoculated with the backbone pCMV vector instead of pCMV-IL-10(pCMV CIA mice), mice inoculated with the pCMV vector alone, without subsequent immunization with CII (pCMV-C mice), and mice not subjected to any treatment (C mice) were examined as controls. At the 3rd and 5th week after 2nd immunization with CII, booster injections of CII in FIA were administered. Foot pad thicknesses were measured weekly and the histopathological changes in the ankle joints and the titers of IgG1 (Th2 type) and IgG2a (Th1 type) isotype antibodies to CII were examined at the 10th week. RESULTS: pCMV-IL-10 CIA mice showed lesser foot pad thicknesses (p < 0.01 except at Weeks 1-3), less severe histopathological changes (p < 0.01 or 0.05) and lower IgG2a/IgG1 ratios of antibodies to CII (p <0.01) than CIA mice. CONCLUSION: Inoculation of pCMV-IL-10 suppressed CIA through suppression of the Th 1 type immune response in CIA, and offers promise as a potential therapeutic strategy for rheumatoid arthritis. | |
| 11350853 | Raised levels of F(2)-isoprostanes and prostaglandin F(2alpha) in different rheumatic dise | 2001 Jun | OBJECTIVE: To evaluate oxidative injury and inflammatory status in various rheumatic diseases by measuring the levels of isoprostanes and prostaglandins in serum and synovial fluid. METHODS: The concentrations of 8-iso-PGF(2alpha) (F(2)-isoprostane indicating oxidative injury) and 15-keto-dihydro-PGF(2alpha) (a major metabolite of prostaglandin F(2alpha)) were measured in both serum and synovial fluid aspirated from 26 patients with various arthritic diseases, including rheumatoid arthritis (RA), reactive arthritis (ReA), psoriatic arthritis (PsA), and osteoarthritis (OA). These prostaglandin derivatives were also measured in serum samples collected from 42 healthy control subjects. RESULTS: Overall, serum levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) were much higher in patients with arthritic diseases than in the healthy control subjects. The levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) in synovial fluid aspirated from knee joints were also high and varied among various types of arthritic patients. Although the synovial fluid level of these prostaglandin derivatives was sometimes higher than in the corresponding serum sample, this was not a consistent finding. Overall, there was no correlation between serum and synovial fluid levels of 8-iso-PGF(2alpha), or between serum and synovial fluid levels of 15-keto-dihydro-PGF(2alpha). However, a strong relation was found between the levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha,) in both serum (r(s)=0.53, p<0.001) and synovial fluid (r(s)=0.62, p<0.001). CONCLUSIONS: These data suggest that both free radical mediated oxidative injury and cyclo-oxygenase dependent inflammatory responses are closely correlated in various types of arthritis. | |
| 9568723 | Transgenic mice expressing a truncated Peromyscus leucopus TNF-alpha gene manifest an arth | 1998 Apr | Several studies have implicated tumor necrosis factor-alpha (TNF-alpha) in autoimmune diseases, such as rheumatoid arthritis (RA). To elucidate further the role of TNF-alpha in inflammatory arthritis, we generated transgenic mice harboring a truncated Peromyscus leucopus TNF-alpha (Pe-TNF) gene. An arthritic phenotype closely resembling human ankylosing spondylitis was observed only in transgenic lines expressing the Pe-TNF transgene at the mRNA level. We characterized the arthritic phenotype in detail by radiographic and histologic techniques. It consisted of severe axial skeletal kyphosis and ankylosis, accompanied by an inflammatory and fibrotic process at the end plates and enthesis. Peripheral joint lesions were absent in mice expressing the P. leucopus TNF-alpha gene, in contrast to the RA-like phenotype described in transgenic mice expressing a truncated human TNF-alpha gene. The Pe-TNF transgenic mouse model provides a unique opportunity to explore potential mechanisms whereby TNF-alpha may initiate an autoimmune arthritis resembling ankylosing spondylitis. | |
| 9775137 | [Frequency of autoimmune diseases in 218 patients with autoimmune thyroid pathologies]. | 1998 Mar | PURPOSE: The aim of our study was to investigate the frequency of auto-immune diseases in patients suffering from autoimmune thyroid diseases. METHOD: We realised a retrospective study from 1981 to 1993 including 218 patients suffering from thyroiditis who were followed in the same hospital service. There were 202 women and 16 men with a mean age 49 at the moment their thyroid pathology was discovered. RESULTS: Thirty patients had one or more autoimmune disease associated to their thyroid disorders, representing 13.7% of total patients. The two most frequent autoimmune diseases were lupus and Sjögren's syndrome. In 17 cases the diagnosis of the associated autoimmune disease was made simultaneously. The systemic disease preceded with an 8-year delay the thyroid disease in five cases, and the thyroid disease was annunciatory in eight cases with a delay of 5 years. The frequency of autoimmune diseases seems to be higher in patients suffering from thyroid disorders than in the general population. They are probably common physiopathological mechanisms. CONCLUSION: The frequency of these associations suggests the need for a long-lasting survey of those patients having thyroid disorders. Initial evaluation and a regular checking in patients suffering from an autoimmune disease is recommenced. | |
| 11469461 | HLA markers and clinical characteristics in Caucasians with primary Sjögren's syndrome. | 2001 Jul | OBJECTIVE: To explore the association between HLA genotypes and clinical and immunological characteristics in Caucasians with primary Sjögren's syndrome (pSS). METHODS: HLA genotyping for DRB1, DQA1 and DQB1 was carried out in 62 single case patients with pSS and 64 healthy controls. The specific amino acid residues at DQA1 position 34 (DQalpha-34Q) and DQB1 position 26 (DQbeta-26L) in addition to the DQ-DI (AA59-AA69) motif were deterrmined. Subsequently, the relative contribution of individual HLA markers to clinical and immunologic characteristics of pSS was assessed by group comparisons. RESULTS: No significant associations were seen between HLA markers and histopathological or clinical features of pSS. Significant positive associations with HLA Class II markers were restricted to the formation of different autoantibodies. Formation of an anti-Ro/SSA and anti-La/SSB autoantibody response was positively associated with DRB1*03, DQB1*02 and DRB1*03/DRB1*15-DQB1*02/DQB1*0602 heterozygosity. Patients positive for anti-La/SSB also showed a strong positive anti-La/SSB association with DQA1*0501. Considering the contribution of individual DQA1 and DQB1 amino acids and sequence motifs to the formation of anti-Ro/SSA and anti-La/SSB autoantibodies, a dose dependent positive influence was detected for DQalpha-34Q and DQbeta-26L. For DQbeta-DI, the largest difference between patients and controls was seen for the presence of a single copy of this motif after selecting patients with either anti-Ro/SSA or anti-La/SSB autoantibodies. CONCLUSION: The association of HLA Class II markers with pSS may concern the anti-Ro/La response rather than the disease itself. The strongest contributors to the formation of an anti-Ro/La response included components of the DRB1*03-DQB1*02-DQA1*0501 haplotype also encompassing the transethnically-associated DQbeta-DI motif. In addition, the dose dependent contribution of DQalpha-34Q and DQbeta-26L argue for a recessive contribution of HLA-DQ to the formation of an anti-Ro/La response. Given the prominent associations with DRB1*03 and the complex dose dependent interactions at HLA-DQ, a joint contribution of HLA-DR and DQ is likely to be relevant for the formation of anti-Ro/La autoantibodies in patients with pSS. | |
| 10609075 | Acute dysautonomia secondary to autoimmune diseases: efficacy of intravenous immunoglobuli | 1999 Nov | Acute dysautonomia is a disorder characterized by severe sympathetic and parasympathetic failure with relative preservation of motor and sensory function. The disease is considered to be idiopathic in most cases, but there is now a trend towards considering the disorder as an uncommon variant of Guillain Barré syndrome. We report two cases of acute dysautonomia which did not fulfill the criteria of the idiopathic form. The first case was associated with Sjögren's syndrome and the second with thyroiditis and antiganglioside antibodies which were correlated with the severity of the disease. Intravenous gammaglobulin (IVGG) was effective in both cases, as has been reported for the idiopathic form, and in one case the treatment was associated with an increase in the supine and standing plasma norepinephrine levels, thus substantiating the positive effects of IVGG on the orthostatic blood pressure and heart rate. We conclude that the spectrum of acute dysautonomia is superimposable on that of the inflammatory peripheric neuropathies and should include both the idiopathic form and dysautonomia with autoimmune associated disorders. IVGG are effective and seems to act by increasing plasma norepinephrine levels. | |
| 9644745 | [Clinical and laboratory characteristics of patients with Sjogren's disease lasting from y | 1998 | AIM: Characterization of Sjogren's disease (SD) with onset at early age basing on the comparison of two patient groups--with the disease onset at the age under 30 and over 50. MATERIALS AND METHODS: Clinical, ophthalmological and stomatological examinations were performed in 31 SD patients who developed the disease at the age under 30 (group 1) and over 50 (group 2). RESULTS: In group 1 the disease started with parotitis in 42.8% of cases, dysfunction of secreting epithelial glands was rare, functional activity of exocrine glands was normal, dysproteinemia (high total protein levels, hypergammaglobulinemia, hypoalbuminemia) and immunological defects (high levels of circulating immune complexes, rheumatoid factor, antinuclear factor) were more pronounced. At retrospective analysis not only a decline of functional activity of the salivary and lacrimal glands but also appearance of systemic symptoms were registered. CONCLUSION: Development of systemic SD symptoms at young age necessitates early pathogenetic therapy employing corticosteroid, cytostatic and other drugs. |