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1.
Drugs Today (Barc) ; 56(11): 723-732, 2020 11.
Article in English | MEDLINE | ID: mdl-33332480

ABSTRACT

In rheumatoid arthritis (RA) there is an unmet therapeutic need, as a substantial proportion of patients does not achieve low disease activity or remission despite the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or biological DMARDs (bDMARDs). The Janus kinase (JAK) inhibitors are the most recently added drug category in the therapeutic armamentarium in RA. Upadacitinib tartrate (Rinvoq), a selective and reversible JAK1 inhibitor, inhibited interleukin (IL)-6 and IL-7 and ameliorated adjuvant-induced arthritis in preclinical studies. In phase III randomized controlled trials (RCTs), upadacitinib, as monotherapy or in combination with csDMARDs, showed efficacy in RA patients with inadequate response to csDMARDs or bDMARDs. In a head-to-head RCT, upadacitinib 15 mg once daily was superior to adalimumab in achieving remission and in patient-reported outcomes. Upadacitinib has a good safety profile but it may increase the risk for herpes zoster, and as a substrate of cytochrome P450 (CYP) enzyme CYP3A4 it should not be coadministered with strong CYP3A4 inducers. Upadacitinib is contraindicated in patients with active tuberculosis, serious infections, active malignancy and in patients with severe liver impairment. Upadacitinib has been approved for the treatment of moderate to severe RA.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Heterocyclic Compounds, 3-Ring/pharmacology , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Methotrexate/therapeutic use , Tartrates/therapeutic use
2.
Br J Dermatol ; 181(1): 138-146, 2019 07.
Article in English | MEDLINE | ID: mdl-30875084

ABSTRACT

BACKGROUND: Anti-C1q autoantibodies (autoAbs) are associated with systemic lupus erythematosus (SLE), but their presence in other rheumatic diseases has not been adequately investigated. OBJECTIVES: We aimed to assess anti-C1q autoAbs and circulating immune complexes (CICs) in systemic sclerosis (SSc). METHODS: In total 124 patients with SSc were studied; 106 were female and the median age was 59·4 years (range 25-81·4). Overall 75 (60·5%) had limited cutaneous SSc and 49 (39·5%) had diffuse cutaneous SSc. Also included were 25 patients with Sjögren syndrome (SjS), 29 with rheumatoid arthritis (RA), 38 with SLE and 53 healthy controls. Enzyme-linked immunosorbent assays with high- and low-salt buffers were used to measure anti-C1q antibodies and CICs. The former allows only anti-C1q antibody binding to C1q and the latter also allows IgG Fc to bind to C1q. RESULTS: Anti-C1q antibodies were present in 20 of 124 (16·1%) patients with SSc: five had high levels (> 80 RU mL-1 ) and 10 (50%) had moderate levels (40-80 RU mL-1 ). Anti-C1q antibodies were also present in one of 25 (4%) patients with SjS, one of 29 (3%) with RA (P < 0·05 for both) and three of 53 (6%) healthy controls (P < 0·01). Anti-C1q antibodies were detected in 13 of 38 (34%) patients with SLEs. Anti-C1q antibodies were more frequent in male than female patients with SSc (P = 0·005); this association remained after multivariate regression analysis. Anti-C1q antibody level was the most important factor in predicting the presence of pulmonary fibrosis, and the second most important in predicting pulmonary arterial hypertension. Fourteen patients with SSc (11·3%) had CICs. CONCLUSIONS: Anti-C1q autoAbs were frequently detected in patients with SSc, and their high levels predict the co-occurrence of pulmonary fibrosis or pulmonary arterial hypertension.


Subject(s)
Autoantibodies/blood , Autoantigens/immunology , Complement C1q/immunology , Pulmonary Fibrosis/blood , Scleroderma, Systemic/complications , Adult , Aged , Aged, 80 and over , Autoantibodies/immunology , Cohort Studies , Female , Healthy Volunteers , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Pulmonary Fibrosis/diagnosis , Pulmonary Fibrosis/immunology , Scleroderma, Systemic/blood , Scleroderma, Systemic/immunology , Sex Factors , Tomography, X-Ray Computed
3.
Oral Dis ; 23(7): 828-839, 2017 Oct.
Article in English | MEDLINE | ID: mdl-27717092

ABSTRACT

To date, there is a major effort in deciphering the role of complex microbial communities, especially the oral and gut microbiomes, in the pathogenesis of various diseases. Increasing evidence indicates a key role for the oral microbiome in autoimmune diseases. In this review article, we discuss links of the oral microbiota to a group of autoimmune diseases, that is, Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), Crohn's disease (CD), and rheumatoid arthritis (RA). We particularly focus on factors that affect the balance between the immune system and the composition of microbiota leading to dysbiosis, loss of tolerance and subsequent autoimmune disease progression and maintenance.


Subject(s)
Arthritis, Rheumatoid/immunology , Crohn Disease/immunology , Gastrointestinal Microbiome/immunology , Lupus Erythematosus, Systemic/immunology , Mouth/microbiology , Sjogren's Syndrome/immunology , Autoimmunity , Dysbiosis/immunology , Humans
4.
Lupus ; 24(4-5): 364-73, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25801879

ABSTRACT

The exposome represents all exogenous and endogenous environmental exposures that begin at preconception and carry on throughout life, while the microbiome reflects the microbial component of the exposome. We recently introduced the concept of infectome and autoinfectome as a means of studying the totality of infections throughout life that participate in the induction as well as the progression of autoimmune diseases in an affected individual. The investigation of the autoinfectome could help us understand why some patients develop more than one autoimmune disease, a phenomenon also known as mosaic of autoimmunity. It could also explain the infectious and autoantibody burden of various autoimmune rheumatic diseases. The close interplay between infections and the immune system should be studied over time, long before the onset of autoaggression and autoimmunity. Tracking down each individual's exposure to infectious agents (as defined by the autoinfectome) would be important for the establishment of a causative link between infection and autoimmunity.


Subject(s)
Autoimmunity , Infections/immunology , Microbiota/immunology , Animals , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Arthritis, Rheumatoid/immunology , Autoantibodies/immunology , Environmental Exposure , Humans , Lupus Erythematosus, Systemic/immunology , Scleroderma, Systemic/immunology
5.
Osteoarthritis Cartilage ; 17(10): 1283-7, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19447214

ABSTRACT

OBJECTIVE: Erosive osteoarthritis (OA) (EOA) is considered an aggressive form of primary OA that is defined radiographically by intra-articular erosions of the inter-phalangeal joints of the hand and characteristic deformities. The aim of the present study was the sonographic investigation of hand small joints in patients with EOA and comparison of the imaging findings with conventional radiography (CR). METHOD: Twenty-two patients (20 women, mean age 62.5 years) with clinical and radiographic diagnosis of EOA formed our study group. A total of 660 joints were assessed by both radiographs and ultrasound (US). US and plain films were evaluated by two different physicians on a blinded fashion. Erosions, osteophytes and deformities were evaluated by both US and plain films. Synovial thickening, effusion, and power Doppler signal indicative of abnormal vascularity were recorded in each joint during US scanning. RESULTS: Erosions were detected in 231/660 (35%) small joints by US and in 115/660 (17.4%) small joints by conventional radiographs (P<0.05). Osteophytes were detected in 360/660 (54.5%) small joints by US, and in 310/660 (47.0%) small joints by conventional radiographs (P<0.05). Thickened synovium was detected in 19 of 22 patients and increased intra-articular power Doppler signal, indicative of active inflammation, was detected in 18 of 22 patients. Thickened synovium was found in 159/660 (24.1%), effusion in 119/660 (18%) and increased power Doppler in 148/660 (22.4%) small joints. Intra-observer kappa value for agreement regarding US was 0.81 and plain films 0.86. In 31 instances extensive finger tenosynovitis was also evident. CONCLUSION: In patients with EOA, US is a reliable and a more sensitive imaging modality than CR in detecting erosions and osteophytes. US detects inflammatory changes in small hand joints in the vast majority of patients with EOA and suggests that current treatment modalities are inadequate treatment for this disease.


Subject(s)
Finger Joint/diagnostic imaging , Inflammation/diagnostic imaging , Osteoarthritis/diagnostic imaging , Synovial Membrane/diagnostic imaging , Aged , Female , Finger Joint/pathology , Humans , Male , Middle Aged , Osteoarthritis/physiopathology , Osteophyte/diagnostic imaging , Radiography , Synovial Membrane/pathology , Ultrasonography/methods , Ultrasonography/standards
7.
Transplantation ; 71(8): 1137-46, 2001 Apr 27.
Article in English | MEDLINE | ID: mdl-11374416

ABSTRACT

BACKGROUND: We investigated the role of apoptosis (programed cell death) in the pathogenesis of chronic rejection. METHODS: Epicardial coronary arteries from cardiac allografts with chronic rejection were examined for apoptosis by the TUNEL assay. Double labeling was carried out using anti-CD3, anti-CD68, and anti-von Willenbrand factor (vWF) monoclonal antibodies. Additional immunostaining was carried using anti-Fas, anti-Fas-L, and anti-Bcl-2 monoclonal antibodies. Apoptosis-associated oligonucleosomal DNA degradation was assessed by DNA agarose gel electrophoresis. The transcription level of apoptosis-related caspase genes were determined using microarrays. RESULTS: Apoptotic cells (TUNEL+) were detected within the arterial wall and in perivascular areas. Double labeling demonstrated that apoptotic cells included T cells (CD3+), monocyte/macrophages (CD68+), and vascular endothelial cells (VWF+). Numbers and densities of TUNEL+ cells did not correlate with the degree of arterial stenosis. Apoptosis-associated oligonucleosomal DNA degradation was assessed by agarose gel electrophoresis of DNA, which showed DNA fragments of approximately 180 bp and multimers thereof (DNA laddering gel), which are characteristic for DNA fragmentation in apoptotic cells. Microarray analysis demonstrated that the apoptosis related caspases 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, were all transcribed (caspases 8, 9, and 10 were highly up-regulated). These results are consistent with the involvement of apoptosis in chronic rejection. Immunoreactivity for Fas/Fas-L was present at the sites of apoptotic cells. Immunoreactivity for Bcl-2 was present in areas with very few apoptotic cells. CONCLUSIONS: Apoptotic cells include T cells, monocyte/macrophages, and endothelial cells. Apoptosis, likely through the Fas/Fas-L system, is involved in the pathogenesis of chronic rejection in cardiac allografts.


Subject(s)
Apoptosis , Graft Rejection/immunology , Graft Rejection/pathology , Heart Transplantation/immunology , Heart Transplantation/pathology , Adult , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , CD3 Complex/analysis , Chronic Disease , Coronary Vessels/immunology , Coronary Vessels/pathology , DNA Fragmentation , Fas Ligand Protein , Female , Humans , In Situ Nick-End Labeling , Macrophages/immunology , Macrophages/pathology , Male , Membrane Glycoproteins/analysis , Middle Aged , Monocytes/immunology , Monocytes/pathology , Proto-Oncogene Proteins c-bcl-2/analysis , T-Lymphocytes/immunology , T-Lymphocytes/pathology , fas Receptor/analysis
8.
Arch Pathol Lab Med ; 124(4): 535-44, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10747310

ABSTRACT

OBJECTIVE: To study the immunoreactivity profile of the neuron-associated class III beta-tubulin isotype (beta III) in epithelial lung tumors. DESIGN: One hundred four formalin-fixed, paraffin-embedded primary and metastatic lung cancer specimens were immunostained with an anti-beta III mouse monoclonal antibody (TuJ1) and an anti-beta III affinity-purified rabbit antiserum. Paraffin sections from fetal, infantile, and adult nonneoplastic lung tissues were also examined. RESULTS: In the fetal airway epithelium, beta III staining is detected transiently in rare Kulchitsky-like cells from lung tissues corresponding to the pseudoglandular and canalicular but not the saccular or alveolar stages of development. beta III is absent in healthy, hyperplastic, metaplastic, and dysplastic airway epithelium of the adult lung. In contrast, beta III is highly expressed in small cell lung cancer, large cell neuroendocrine carcinoma, and in some non-small cell lung cancers, particularly adenocarcinomas. There is no correlation between expression of beta III and generic neuroendocrine markers, such as chromogranin A and/or synaptophysin, in pulmonary adenocarcinomas. Also, focal beta III staining is present in primary and metastatic adenocarcinomas (to the lung) originating in the colon, prostate, and ovary. beta III is expressed to a much lesser extent in atypical carcinoids and is rarely detectable in typical carcinoids and squamous cell carcinomas of the lung. The distribution of beta III in small cell lung cancer and adenocarcinoma metastases to regional lymph nodes and brain approaches 100% of tumor cells, which is substantially greater than in the primary tumors. CONCLUSIONS: In the context of neuroendocrine lung tumors, beta III immunoreactivity is a molecular signature of high-grade malignant neoplasms (small cell lung cancer and large cell neuroendocrine carcinoma) although its importance in atypical carcinoids must be evaluated further. In addition, beta III may be a useful diagnostic marker in distinguishing between small cell lung cancers and certain non-small cell lung cancers (poorly differentiated squamous cell carcinomas), especially in small biopsy specimens. To our knowledge, beta III is the only tumor biomarker that exhibits a substantially more widespread distribution in poorly differentiated than in better differentiated pulmonary neuroendocrine tumors. However, the significance of beta III phenotypes in non-small cell lung cancer, particularly adenocarcinoma, with respect to neuroendocrine differentiation and prognostic value, requires further evaluation.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Small Cell/pathology , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Lung/cytology , Neuroendocrine Tumors/pathology , Tubulin/analysis , Adult , Amino Acid Sequence , Animals , Antibodies , Antibodies, Monoclonal , Carcinoid Tumor/pathology , Child , Fetus , Humans , Infant , Mice , Molecular Sequence Data , Peptide Fragments/chemistry , Peptide Fragments/immunology , Rabbits , Respiratory Mucosa/cytology
9.
Clin Diagn Lab Immunol ; 6(5): 660-4, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10473513

ABSTRACT

Recent in vitro studies have shown that interleukin 4 (IL-4) induces and gamma interferon (IFN-gamma) inhibits collagen production. To define the TH1(IFN-gamma) and TH2(IL-4) cytokine profiles in systemic sclerosis (Sscl), a disease characterized by widespread fibrosis, we investigated IL-4 and IFN-gamma transcripts in peripheral blood mononuclear cells and plasma protein levels in 13 patients with Sscl. Two previously identified IL-4 transcripts, a full-length transcript and an alternatively spliced (truncated) transcript (designated IL-4delta2), were identified in patients and normal controls. Significantly increased levels of total IL-4 transcripts (full-length plus IL-4delta2 transcripts) were found in patients with Sscl in comparison to those found in healthy controls (P = 0.003), and this increase was primarily due to an increase in the level of the alternatively spliced IL-4delta2 form. The IL-4delta2/full-length-IL-4 transcript ratio was significantly increased in Sscl patients (P < 0.0001, versus healthy controls). Sequencing analysis revealed that the frequency of IL-4 clones carrying the IL-4delta2 transcript was also substantially increased in patients with Sscl. Plasma IL-4 protein levels were increased in Sscl patients compared to those in healthy controls (P = 0.001) and correlated with total IL-4 transcript levels. The up-regulation of the fibrogenic IL-4 (a TH2 cytokine) in Sscl suggests a pathogenic role for IL-4 in this disease.


Subject(s)
Alternative Splicing/immunology , Interleukin-4/genetics , Leukocytes, Mononuclear/immunology , Scleroderma, Systemic/genetics , Scleroderma, Systemic/immunology , Adult , Cloning, Molecular , Female , Gene Expression/immunology , Humans , Interferon-gamma/genetics , Interleukin-4/immunology , Male , Middle Aged , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Scleroderma, Systemic/etiology , Sequence Analysis, DNA , Transcription, Genetic/immunology
10.
Cell Immunol ; 188(2): 105-10, 1998 Sep 15.
Article in English | MEDLINE | ID: mdl-9756640

ABSTRACT

TH1 cytokines have recently been detected in rheumatoid arthritis (RA) and osteoarthritis (OA). For this reason we studied the TH-1-promoting cytokine IL-12 in synovial membranes from patients with RA and OA. IL-12 transcripts and protein were analyzed by reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemistry, respectively. In addition, IL-12 transcripts were quantitated by competitive PCR. IL-12 transcripts (p40) were detected in 8 of 13 patients with RA and in 10 of 18 patients with OA. Their levels did not differ significantly between RA and OA. IL-12 heterodimer protein was detected by immunostaining using an anti-IL-12p70 mAb. Double labeling with anti-IL-12p70 and anti-CD68 mAbs showed that synovial lining cells and monocytes/macrophages expressed IL-12 p70 protein. The presence of IL-12 p70 protein in the synovial membranes of patients with RA and OA suggests that IL-12 may play an important immunoregulatory role in these diseases by perpetuating inflammation.


Subject(s)
Arthritis, Rheumatoid/immunology , Interleukin-12/biosynthesis , Macrophages/metabolism , Osteoarthritis/immunology , Synovial Membrane/metabolism , Adult , Aged , Female , Humans , Immunohistochemistry , Interleukin-12/genetics , Male , Middle Aged , Synovial Membrane/cytology
11.
Clin Diagn Lab Immunol ; 5(4): 430-7, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9665944

ABSTRACT

The synovial membrane in osteoarthritis (OA) often exhibits inflammatory infiltrates, but the role of T cells in these infiltrates is not known. T-cell activation antigens were analyzed by immunohistochemistry, and T-cell cytokine transcripts were measured by competitive PCR in synovial membranes from patients with OA and rheumatoid arthritis (RA). Lymphoid cell aggregates, containing primarily CD3+ T lymphocytes, were found in 65% of patients with OA. Mononuclear cells expressing the activation antigens CD69, CD25, CD38, CD43, CD45RO, and HLA class II were present in both patient groups, although in higher numbers in patients with RA. Interleukin 2 (IL-2) transcripts were found in 10 of 18 patients with OA versus 12 of 13 patients with RA (P = 0.03). Gamma interferon (IFN-gamma) transcripts were detected in 9 of 18 patients with OA versus 10 of 13 patients with RA (not significant), whereas IL-10 transcripts were found in nearly all patients. IL-4 and IL-5 were not detected in any patients. The levels of IFN-gamma and IL-2 transcripts, normalized for T-cell number equivalents, were not statistically different between OA and RA, but the levels of IFN-gamma, normalized for total cell number equivalents, were lower in OA than in RA (P = 0.01). Synovial membranes that expressed IL-2 and IFN-gamma transcripts were more likely to have heavier infiltrations of T cells and cells bearing activation markers than synovial membranes that did not express these cytokines. The presence of activated T cells and TH1 cytokine transcripts in chronic joint lesions of patients with OA suggests that T cells contribute to chronic inflammation in a large proportion of these patients.


Subject(s)
Cytokines/genetics , Osteoarthritis/immunology , Synovial Membrane/immunology , T-Lymphocytes/immunology , Aged , Antigens, CD/metabolism , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Base Sequence , DNA Primers/genetics , Female , Humans , Immunohistochemistry , Male , Middle Aged , Osteoarthritis/genetics , Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/metabolism , Synovial Membrane/metabolism , T-Lymphocytes/metabolism , Transcription, Genetic
12.
Hematopathol Mol Hematol ; 11(1): 29-40, 1997.
Article in English | MEDLINE | ID: mdl-9439978

ABSTRACT

The human leukocyte-function-associated antigen-1 (LFA-1) plays a key role in intercellular adhesion interactions of the immune response. A monoclonal antibody (mab), designated LDA-8, is described that recognizes LFA-1. In contrast to nearly all other anti-LFA-1 mabs, which inhibit cellular aggregation, LDA-8 induces cell-cell aggregation. The LDA-8 mab was generated by immunizing mice with membrane fragments from the Jurkat T-cell line. The LDA-8 mab stained peripheral blood mononuclear cells (PBMC), monocyte-depleted peripheral blood lymphocytes, purified monocytes, and a number of T and B tumor cell lines. The LDA-8 mab induced aggregation of PBMC from normal donors, as well as of cells from T-cell lines (MOLT4 and CEM). Control mabs directed against HLA class 1 or CD4 did not induce aggregation. Aggregation was concentration- and time-dependent. EDTA added to the cultures 1 hour prior to or together with the LDA-8 mab did not inhibit LDA-8-induced aggregate formation. Anti LFA-1 alpha-chain mab added to the cells 1 hour prior to LDA-8 mab, or together with the LDA-8 mab, also did not inhibit LDA-8-induced aggregation. In contrast, anti-LFA-1 beta-chain mab, added to the cells together with or 1 hour prior to the LDA-8 mab, significantly inhibited LDA-8-induced aggregate formation. The LDA-8 mab immunoprecipitated two polypeptide chains of 110 kDa and 160 kDa under non-reducing conditions and of 92 kDa and 162 kDa under reducing conditions, from cells of the MOLT-4 or CEM T-cell lines or phytohemagglutinin (PHA)-stimulated PBMC. The molecular mass of these polypeptides was identical to that of polypeptides immunoprecipitated by the anti-LFA-1 TS1.22 mab, suggesting that the LDA-8 mab and the anti-LFA-1 mab recognize the same molecule. This was confirmed by sequential immunoprecipitation. The LDA-8 mab recognizes a unique epitope on LFA-1 and induces cell aggregation that is blocked by mabs recognizing the beta-chain, but not the alpha-chain of the LDA-1 molecule.


Subject(s)
Antibodies, Monoclonal/immunology , Lymphocyte Function-Associated Antigen-1/immunology , Lymphocytes/pathology , Animals , Antibodies, Monoclonal/pharmacology , Cell Aggregation/drug effects , Cell Aggregation/immunology , Humans , Lymphocytes/drug effects , Lymphocytes/immunology , Mice
13.
Am J Med Sci ; 310(6): 223-5, 1995 Dec.
Article in English | MEDLINE | ID: mdl-7503100

ABSTRACT

In recent reports, researchers described an increased incidence of cancer in patients with systemic sclerosis (SScl). For this article, the authors investigated the frequencies of cancer in first-degree relatives of patients with SScl in a case-control family study. Information was obtained by personal interview of the probands. Fifty-three subjects with cancer were reported among 814 relatives of patients, compared with 17 subjects among 860 relatives of age- and sex-matched control subjects (age and sex adjusted odds ratio = 3.79, 95% confidence interval = 2.16-6.66, P < 0.001). Forty-six patients (27.7%) had one or more relatives with cancer, compared with 15 control subjects (9%). Within the limitations of the methods used, the researchers found an increased risk for cancer in first-degree relatives of patients with SScl. This suggests that a common genetic or environmental factor may be involved in the development of both cancer and SScl.


Subject(s)
Neoplasms/epidemiology , Scleroderma, Systemic/complications , Adult , Case-Control Studies , Family Health , Female , Humans , Logistic Models , Male , Middle Aged , Neoplasms/complications , Neoplasms/genetics , Odds Ratio , Risk Factors , Scleroderma, Systemic/genetics
15.
Immunol Res ; 14(3): 218-36, 1995.
Article in English | MEDLINE | ID: mdl-8778211

ABSTRACT

Juvenile rheumatoid arthritis (JRA) is defined as chronic arthritis of unknown etiology appearing in patients less than 16 years of age. The disease is heterogeneous and is classified as pauciarticular, polyarticular, or systemic-onset disease. A few lines of evidence suggest that T cells are involved in the pathogenesis of the disease. T cells infiltrating the synovial membrane bear markers of activation and produce cytokines. The association of particular subtypes of JRA with certain HLA class II alleles provides strong evidence in favor of T cell involvement through an HLA-peptide-T cell receptor complex. Limited data from a few patients with JRA on T cell receptor transcripts from synovial membrane or synovial fluid cells point towards oligoclonality. This further supports the concept that T cells infiltrating the synovial membrane or extravasating into synovial fluid in patients with JRA reflect antigen-driven T cell proliferation.


Subject(s)
Arthritis, Juvenile/immunology , Histocompatibility Antigens Class II/immunology , T-Lymphocytes/immunology , Adolescent , Arthritis, Juvenile/microbiology , Bacterial Infections/immunology , Child , Child, Preschool , Cytokines/biosynthesis , Female , Humans , Infant , Lymphocyte Activation , Male , Receptors, Antigen, T-Cell/immunology , Synovial Fluid/immunology , Synovial Membrane/immunology , T-Lymphocytes/metabolism
17.
Immunol Res ; 13(2-3): 117-38, 1994.
Article in English | MEDLINE | ID: mdl-7775804

ABSTRACT

Rheumatoid arthritis (RA) is a systemic disease of unknown etiology characterized by chronic inflammation mainly in the joints. Several lines of evidence suggest that T cells are involved in the pathogenesis of the disease. RA is associated with certain HLA-DR alleles. Studies analyzing T-cell receptor transcripts in RA have found biased or preferential usage of certain V alpha and/or V beta gene segments by T cells infiltrating the synovial membrane or extravasating into the synovial fluid compared to peripheral blood. In certain patients few T-cell antigen receptor (TCR) clones dominated the infiltrating T cells, suggesting that T cells from the synovial membrane or the synovial fluid comprise oligoclonal populations of T cells. However, other studies have found a polyclonal population of T cells. In interpreting these results the phase of the disease (early vs. late RA), the source of T cells and the limitations of the methods used in these studies should be taken into consideration. However, it appears that synovial T cells comprise oligoclonal populations of T cells and that there is a bias towards particular TCR gene segments, although a specific TCR gene segment in RA has not emerged.


Subject(s)
Arthritis, Rheumatoid/immunology , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , Base Sequence , Cell Line , Humans , Molecular Sequence Data , Polymorphism, Genetic/genetics , Synovial Fluid/immunology , Synovial Membrane/immunology , Transcription, Genetic/genetics
18.
Ann Rheum Dis ; 52(4): 300-1, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8484697

ABSTRACT

OBJECTIVES: To elucidate the role of HLA-DRB, -DQA, and -DQB genes in patients with rheumatoid arthritis (RA) who developed gold induced nephropathy. METHODS: Southern blot analysis of HLA-DRB, -DQA, and -DQB genes was performed on DNA from 27 patients with RA with gold induced nephropathy, 37 patients with RA who were treated with gold but did not develop nephropathy, and 122 ethnically matched normal subjects. RESULTS: The 4.7 kb DQA1/Taq I band associated with DQA1*0501 and DR3 and DR5 was found in 16 (59%) patients with gold induced nephropathy compared with five (14%) patients without gold induced nephropathy. CONCLUSION: It is concluded that HLA-DQA region genes may be an important susceptibility factor for the development of gold induced nephropathy in patients with RA.


Subject(s)
Arthritis, Rheumatoid/genetics , Genes, MHC Class II/physiology , Gold Sodium Thiomalate/adverse effects , Kidney Diseases/chemically induced , Kidney Diseases/genetics , Base Sequence , Female , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Humans , Male , Molecular Sequence Data , Polymerase Chain Reaction
19.
J Intern Med ; 232(3): 279-82, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1402626

ABSTRACT

Five patients with Wegener's granulomatosis (WG) have been treated with 6- to 8-monthly pulses of intravenous cyclophosphamide (CP) and glucocorticoids in an open pilot study. One patient achieved complete remission sustained during 30 months of follow-up; one patient had features of active disease after 28 months of remission; two patients after an initial remission had an exacerbation of the disease and received continuous oral administration of CP, and one patient required continuous oral CP to control the symptoms. These results suggest that this regimen may not achieve a high degree of sustained remission in patients with WG.


Subject(s)
Cyclophosphamide/administration & dosage , Granulomatosis with Polyangiitis/drug therapy , Administration, Oral , Adolescent , Adult , Aged , Cyclophosphamide/therapeutic use , Drug Administration Schedule , Humans , Infusions, Intravenous , Male , Middle Aged , Pilot Projects , Treatment Outcome
20.
Br J Rheumatol ; 30(6): 449-50, 1991 Dec.
Article in English | MEDLINE | ID: mdl-1684125

ABSTRACT

A polymorphism of the switch region of the mu IgH gene (S mu) is associated with arthritis in English patients with psoriasis. In this study, Italian patients with psoriasis alone (PS) or psoriatic arthritis (PSA) were analysed by Southern blot using DNA probes for the S mu region and a hypervariable locus 5' of the joining (JH) region of IgH (5' JH). No association between PSA and IgH gene polymorphisms was found. However, an association was found between PS and a genotype of the 5' JH region (Fisher's P = 0.0002, RR = 27). Additional DNA markers around the S mu region may reveal more accurate markers for PS or PSA.


Subject(s)
Arthritis, Psoriatic/genetics , Genes, Immunoglobulin/genetics , Polymorphism, Genetic , Psoriasis/genetics , Arthritis, Psoriatic/immunology , Chi-Square Distribution , Humans , Immunoglobulin Switch Region/genetics , Italy , Polymorphism, Restriction Fragment Length , Psoriasis/immunology , Risk
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