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ID PMID Title PublicationDate abstract
8509157 Clinical relevance of antibodies to Ro/SS-A and La/SS-B in subacute cutaneous lupus erythe 1993 Apr Ro/SS-A autoantibodies are frequently associated with subacute cutaneous lupus erythematosus, neonatal lupus erythematosus and Sjögren's syndrome. The Ro/SS-A autoantigen is a ribonucleoprotein complex consisting of at least four protein components and four small cytoplasmic RNA components designated hY RNA 1, 3, 4 and 5. Three of the Ro/SS-A peptides have been isolated and cloned. The function of this ribonucleoprotein complex is as yet unknown.
8804464 The relevance of VDJ PCR protocols in detecting B-cell clonal expansion in lymphomas and o 1995 Nov AIMS AND BACKGROUND: The detection of immunoglobulin heavy chain variable (VH)-diversity (DH)-joining (JH) region gene rearrangement by polymerase chain reaction (VDJ PCR) has been recently proposed as a rapid approach to assess B-cell clonality in lymphoproliferative disorders. The aim of the present study was to determine the efficacy of VDJ PCR in a wide spectrum of lymphoproliferative disorders previously characterized by immunohistochemistry and Southern blot (SB). METHODS: 83 SB-rearranged B-cell non-Hodgkin's lymphomas (NHL) of different histotype, 22 cases of SB-unrearranged classical Hodgkin's disease (HD), 18 cases of HIV-related reactive lymphadenopathy, and 4 frankly pre-lymphomatous lesions (MESA) in the course of Sjögren's syndrome were investigated by 2 different VDJ PCR protocols (FR3, FR2). RESULTS: The detection rate in NHL was 64% and 71% using the protocols FR3 and FR2, respectively. However, the overall VDJ PCR efficacy increased to 81% by combining the results of both protocols. In addition, differences in the combined, as well as in the single FR3 or FR2 protocol efficacy, were noted in the different NHL subgroups. B-cell clonality was also detected in 4/22 (18%) SB-unrearranged classical HD cases and in 2/18 (11%) reactive lymphadenopathy cases, whereas it was demonstrated in all the MESA lesions, 2 of them being SB-negative. CONCLUSIONS: VDJ PCR represents a useful and rapid technique to detect B-cell clonality in NHL, although with some differences depending on the NHL histotype and the panel of primers employed. The technique may also be of value to investigate the possible progression of early B-cell clonal expansion into frankly B-cell malignancy and to contribute to the controversy about the clonal lineage origin of the putative HD malignant cells.
7962607 Immunoreactivity of neoplastic and non-neoplastic monocytoid B lymphocytes for DBA.44 and 1994 Oct AIMS--To evaluate the immunoreactivities of neoplastic and non-neoplastic monocytoid B cells (MBC) and compare them with hairy cell leukemia (HCL) and mantle cell lymphoma (MCL). METHODS--An immunohistochemical study of paraffin wax embedded sections was done on surgically resected specimens of spleens with MBC clusters from patients with gastric cancer (14 cases), tonsils (five cases), and lymph node (two cases) showing lymphoid follicular hyperplasia (LFH), submandibular lymph nodes containing MBC in Sjögren's syndrome (one case). Extranodal organs affected by MCL (three cases) and monocytoid B cell lymphoma (MBCL) (seven cases), and spleens from HCL (four cases) were also studied. These specimens were fixed in 10% formalin and routinely processed for paraffin wax embedding. Fresh spleen specimens from patients with liver cirrhosis (one case) and gastric cancer (seven cases) were snap frozen. RESULTS--Mantle zone lymphocytes were DBA.44, CD74 positive and showed a weaker reaction for CDw75 than marginal zone lymphocytes and MBC, which were almost DBA negative. In neoplastic diseases tumour cells in MCL were DBA.44, CD74, and CDw75 positive. MBCL showed a positive reaction for CD74 and CDw75, but positivity for DBA.44 was observed in only one of seven cases. The HCL specimens, all positive for DBA.44, showed a weaker reaction for CD74 and a stronger reaction for CDw75 than either MCL and MBCL specimens. CONCLUSION--These results show that mantle zone lymphocytes and MCL more closely matched HCL for reactivity to DBA.44 than MBC and MBCL. Reactivities for DBA.44 and CDw75 were greater in MBCL compared with its non-neoplastic counterpart, MBC.
20301357 WAS-Related Disorders. 1993 CLINICAL CHARACTERISTICS: The WAS-related disorders, which include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked congenital neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes caused by pathogenic variants in WAS. WAS-related disorders usually present in infancy. Affected males have thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; eczema; and recurrent bacterial and viral infections, particularly of the ear. At least 40% of those who survive the early complications develop one or more autoimmune conditions including hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, rheumatoid arthritis, vasculitis, and immune-mediated damage to the kidneys and liver. Individuals with a WAS-related disorder, particularly those who have been exposed to Epstein-Barr virus (EBV), are at increased risk of developing lymphomas, which often occur in unusual, extranodal locations including the brain, lung, or gastrointestinal tract. Males with XLT have thrombocytopenia with small platelets; other complications of Wiskott-Aldrich syndrome, including eczema and immune dysfunction, are usually mild or absent. Males with XLN have congenital neutropenia, myeloid dysplasia, and lymphoid cell abnormalities. DIAGNOSIS/TESTING: The diagnosis of a WAS-related disorder is established in a male proband with both congenital thrombocytopenia (<70,000 platelets/mm(3)) and small platelets, in addition to at least one of the following features: eczema, recurrent bacterial or viral infections, autoimmune disease(s), malignancy, reduced WASP expression in a fresh blood sample, abnormal antibody response to polysaccharide antigens and/or low isohemagglutinins, or positive maternal family history of a WAS-related disorder. Identification of a hemizygous WAS pathogenic variant on molecular genetic testing is necessary to confirm the diagnosis. MANAGEMENT: Treatment of manifestations: Treatment options depend on an individual's predicted disease burden; hematopoietic cell transplantation (HCT) is the only known curative treatment. Topical steroids for eczema; antibiotics for infected eczema; judicious use of immunosuppressants for autoimmune disease; granulocyte colony stimulating factor (G-CSF) and appropriate antibiotics for neutropenia. Prevention of primary manifestations: Pneumocystis jiroveci (formerly known as Pneumocystis carinii pneumonia, or PCP) prophylaxis with Bactrim(®) (trimethoprim-sulfamethoxazole) or pentamidine, intravenous immunoglobulin (IVIgG) replacement therapy, routine childhood "non-live" immunizations; judicious use of platelet transfusions for significant bleeding and surgical procedures. Surveillance: Routine monitoring of blood counts and adequacy of IVIgG replacement therapy. Agents/circumstances to avoid: Circumcision of at-risk newborn males who have thrombocytopenia; use of medications that interfere with platelet function. Defer elective procedures until after HCT. Evaluation of relatives at risk: Evaluation of at-risk newborn males so that morbidity and mortality can be reduced by early diagnosis and treatment. GENETIC COUNSELING: WAS-related disorders are inherited in an X-linked manner. If the mother is a carrier of a WAS pathogenic variant, the chance of transmitting the pathogenic variant in each pregnancy is 50%: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers. Males will pass the pathogenic variant to all of their daughters and none of their sons. Female carriers of a WAS pathogenic variant are usually asymptomatic and have no immunologic or biochemical markers of the disorder. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variant has been identified in the family.
8806790 Effector mechanism of experimental autoimmune sialadenitis in the mouse model for primary 1996 Aug 1 We have recently established a new animal model for primary Sjögren's syndrome in NFS/sld mutant mice thymectomized 3 days after birth (3dTX) bearing an autosomal recessive gene with sublingual gland differentiation arrest. In this study, we analyze developing mechanisms of experimental autoimmune sialadenitis (EAS) in the mouse model, focusing on local expressions of cytokine and cell adhesion molecule genes by reverse transcriptase-polymeric chain reaction (RT-PCR) and immunohistochemistry, kinetic analysis of splenic lymphocytes expressing activation markers, and I-Aq class-II molecules by flow cytometry (FACS). We found up-regulation of local cytokine genes (IL-1 beta, TNF-alpha, IL-2, IFN-gamma, IL-6, IL-10, IL-12p40) and cell adhesion molecule genes (ICAM-1, LFA-1, CD44, Mel-14) in the salivary glands from mice with EAS by RT-PCR, which were supported by immunohistochemistry. FACS analysis demonstrated that a significant proportion of splenic CD4+ T cells express activation markers (CD44, LFA-1, Mel-14low, CD45RB(low)) at a high level and an increase in expression of B220+ B cells bearing I-Aq class-II molecules. These data suggest that spontaneous EAS in 3dTX NFS/sld mutant mice may be triggered by an in situ activation of autoreactive CD4+ T cells comprising unique cytokine profile (high levels of IL-2, IFN-gamma, IL-10, and IL-12p40 mRNA) in the salivary glands.
8702447 Cytokine messenger RNA expression in the labial salivary glands of patients with Sjögren' 1996 Aug OBJECTIVE: To characterize the initiation and progress of localized autoimmune damage in Sjögren's syndrome (SS), an autoimmune disease that is also considered to be a lymphoaggressive disorder, by examining the pattern of cytokine production at the site of autoimmune damage. METHODS: Using a polymerase chain reaction-based method, cytokine messenger RNA (mRNA) expression in the labial salivary glands of 15 patients with SS was investigated. In addition, the infiltrating lymphocytes in the labial salivary glands were examined immunohistochemically. RESULTS: Messenger RNAs of Th1 cytokines, such as interleukin-2 (IL-2) and interferon-gamma, were consistently detected in all patients, while Th2 cytokine mRNAs, such as IL-4 and IL-5, were detected in some cases, in association with strong B cell accumulation in the labial salivary glands. Other cytokine mRNAs produced by a variety of cell types, including IL-10, IL-6, and transforming growth factor beta (TGF beta), were also consistently detected in all patients, while IL-12 mRNA was detected in some of the patients. CONCLUSION: These results suggest that Th1 cytokines, as well as IL-10, IL-6, and TGF beta, are essential in the induction and/or maintenance of SS, while Th2 cytokines are involved in the progression of the disease process, especially local B cell activation.
1373197 Target epitope in the Tax protein of human T-cell leukemia virus type I recognized by clas 1992 May A trans-acting regulatory gene product p40tax (Tax) of human T-cell leukemia virus type I (HTLV-I) is one of the main target antigens recognized by cytotoxic T lymphocytes (CTL) specific for HTLV-I. A CTL epitope within the Tax protein was identified in this report. HTLV-I-specific CD8+ CTL lines established from two HTLV-I carriers with HTLV-I-associated myelopathy or Sjögren syndrome were previously demonstrated to kill predominantly the target cells expressing HTLV-I Tax. The CTL from two patients showed significant levels of cytotoxicity to autologous target cells pulsed with a synthetic peptide of 24 amino acids corresponding to the amino-terminal sequences of the Tax protein. Allogeneic target cells were also sensitized for CTL by this peptide when the target cells have HLA-A2. Tax-specific cytotoxicity, detected as cytolysis of the target cells infected with vaccinia virus-HTLV-I recombinant expressing Tax protein, was almost completely inhibited by competitor cells pulsed with the synthetic peptide. This indicates that a major CTL epitope is present in this peptide. Further analysis using shorter peptides revealed that the core sequence of the CTL epitope was LLFGYPVYV at positions 11 through 19. This sequence can be aligned with the HLA-A2-specific motifs reported recently.
8722363 Absence of cytomegalovirus and Epstein-Barr virus expression in labial salivary glands of 1996 Apr We investigated in 15 consecutive patients a possible correlation between expression of CMV or EBV in labial salivary gland (LSG) biopsies performed 100 days after allogeneic BMT and subsequent development of chronic GVHD. Three techniques were performed for the detection of each virus: immunohistochemistry, in situ hybridization and PCR. Eleven patients developed chronic GVHD. Histologic examination detected a moderate lymphoid infiltrate (grade 1 according to Sale's score) in LSG biopsy in only one patient. CMV genes or proteins could not be detected in any patients. Likewise, EBV genome or proteins were not detected by in situ hybridization and immunohistochemistry. However, in three of the 15 patients, EBV DNA was detected by PCR in LSG biopsies. Only one of these three patients developed chronic GVHD. Therefore, at the present time, the presence of a lymphoid infiltrate on lip biopsies performed at day 100 post-BMT does not appear to be sensitive enough for the diagnosis or the prediction of the subsequent development of chronic GVHD. Moreover, the absence of EBV and CMV expression in a day-100 LSG biopsy does not preclude the development of chronic GVHD.
8839832 A variant CD30 protein lacking extracellular and transmembrane domains is induced in HL-60 1996 Oct 1 We identified and cloned cDNAs for two novel CD30 mRNAs of 2.3 kb that are induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in the human myeloid leukemia cell line HL-60. These transcripts were transcribed from the intronic region just upstream of the exon coding for the transmembrane domain of the CD30 protein. The shorter cDNA had a deletion of 54 nucleotides corresponding to the 3' region of the transmembrane domain of the CD30 and which was probably caused by alternative splicing. Translation of these transcripts appeared to start from the internal methionine codon at nucleotide position 289 that corresponds to that of 1612 in the CD30 cDNA, and encode a protein of 132 amino acid residues which corresponds exactly to the C-terminal cytoplasmic domain of CD30 protein. The calculated molecular mass of this variant CD30 (CD30v) protein was 14,087. Thus, the predicted CD30v protein retains most of the cytoplasmic region, but lacks the extracellular and transmembrane domains. Northern blots detected the expression of CD30v transcripts only in the lung and the TPA-stimulated HL-60 cell line. Translation of this mRNA in vitro produced a protein of 25 kD. Immunoblotting analysis with HCD30C1, a rabbit polyclonal antibody raised against the cytoplasmic domain of CD30 protein, detected proteins with an apparent Mr 25 kD expressed in TPA-stimulated HL-60 and COS-7 cells that were transfected with both types of CD30v cDNAs. Constitutive phosphorylation of the CD30v protein was demonstrated by in vitro labeling with [32P]. Immunohistochemical studies demonstrated CD30v protein was in alveolar macrophages. Cotransfection experiments using a kappa B-site-dependent reporter construct showed that CD30v can transactivate gene expression through activation of NF kappa B, as was noted on the authentic CD30 protein. Overexpression of the CD30v induced differentiation of HL-60 cells as evidenced by an increased NBT reduction activity. These observations provided new insights into the molecular heterogeneity and biological function of CD30 in myeloid cells.
8861523 Extrahepatic manifestations of hepatitis C. 1996 May Shortly after the discovery of the hepatitis C virus, it was realized that this infectious agent caused more than just liver disease. A remarkable array of extrahepatic manifestations of hepatitis C has now been described. Many of these associated syndromes implicate the hepatitis C virus as a mediator of autoimmunity or of immune complex formation. These disorders include mixed essential cryoglobulinemia, autoimmune hepatitis, glomerulonephritis, thyroiditis, and possibly Sjogren's syndrome. The hepatitis C virus has also been strongly linked to two skin disorders: prophyria cutanea tarda and lichen planus. Other possible hepatitis-C-associated diseases described in the literature include idiopathic pulmonary fibrosis, IgA deficiency. Mooren's corneal ulcers, Behcet's syndrome, polyarthritis, Guillain-Barre' syndrome, idiopathic thrombocytopenic purpura, and others. A number of these reported diseases have either responded to or been cured by a therapeutic course of alpha interferon. This report discusses the reported extrahepatic manifestations of hepatitis C as of mid-1995.
11567728 Rheumatoid arthritis. 2001 Sep 15 Rheumatoid arthritis is a systemic inflammatory disorder that mainly affects the diarthrodial joint. It is the most common form of inflammatory arthritis, and has a substantial societal effect in terms of cost, disability, and lost productivity. Although the pathogenesis of rheumatoid arthritis remains incompletely understood, much insight into the cellular and molecular mechanisms involved has been gained in the past decade. On the basis of these insights, new therapies have been developed, and clinical trials have shown the efficacy of aggressive treatment of patients with active disease. In this review, we discuss improvements in our understanding of the pathophysiology of inflammatory synovitis in rheumatoid arthritis, and improvements in therapy for patients with the disorder. The past decade has seen substantial advances in these areas. Future studies will be directed at improving methods for early diagnosis and identification of patients with progressive disease, and at improving methods to identify candidates for subclasses of disease-modifying antirheumatic drugs (DMARDs). Long-term safety and efficacy data for the new DMARD agents and combination regimens will also further delineate efficacy and toxicity and thus the appropriate clinical context for use of these therapeutic approaches. The continuing elucidation of pathophysiological pathways relevant in rheumatoid arthritis, coupled with continuing advances in biotechnology and rational drug design, offer substantial hope for the continued development of increasingly potent and specific pharmacotherapy for treatment of rheumatoid arthritis.
10652640 Established rheumatoid arthritis. 1999 Dec Currently the diagnosis of rheumatoid arthritis (RA) may be difficult; the ACR criteria appear most sensitive and specific in long-standing disease. Without clear definition or diagnostic criteria for early disease it is difficult to define late or established RA. The distinction between early and established RA has been further blurred by recent imaging studies that suggest even in what is currently termed early disease, there is evidence of joint damage. The natural history of RA suggests that most patients with clinic-diagnosed RA have a progressively disabling course, but evidence is growing that modern therapeutic strategies result in better long-term outcomes, especially when applied early in the disease course. In established disease, quantitative markers such as C-reactive protein (CRP) give prognostic information, but in the pre-erosive, early phase of the disease the qualitative markers such as rheumatoid factor (RF) and shared epitope are crucial. As rheumatologists, our major aims must remain: (1) to diagnose the disease as early as possible; (2) to identify those patients with poor prognosis who will benefit most from targeted therapy; and (3) to aim for more intensive disease control irrespective of disease duration.
10989510 Elderly-onset rheumatoid arthritis. 2000 Aug It is appreciated that age has a modifying effect on the clinical presentations of disorders such as hyperthyroidism and systemic lupus erythematosus. Similarly in EORA, there seems to be a change in the disease phenotype when it is compared to YORA. These differences are significant not only in highlighting the importance of the aging process on the immune system but also because they have medical and therapeutic implications. Improved classification has greatly improved our understanding and treatment of systemic lupus erythematosus, juvenile chronic arthritis, and seronegative spondyloarthropathies. Similarly, appreciating the differences, and similarities, between YORA and EORA should advance the choice of therapeutic options and potentially move closer to defining pathogenesis and origin.
10433401 Rheumatoid arthritis in the elderly. 1999 Jun Rheumatoid arthritis of late onset (LORA) referred as the subset of rheumatoid arthritis with age of onset over 60 years old, seems to differ from young onset disease (YORA) by a more equal sex distribution, a higher frequency of abrupt disease onset, more large joint complaints and less extraarticular features. Different immunogenetic associations are also reported between the two age groups. The percentages of rheumatoid factor (RF) and C-reactive protein (CRP) positivity differ in various surveys in both groups examined. Favorable prognostic factors could be considered the absence of rheumatoid factor activity and the presence of pitting edema of the hands. Greek patients with LORAS appear not to have differences in comparison to their younger counterparts. Disease modifying drugs and low doses of prednisone are the mainstream of therapy with need for further caution in the aged group.
10405518 Rheumatoid arthritis and primary care: the case for early diagnosis and treatment. 1999 Jun Rheumatoid arthritis is a chronic inflammatory disease that can cause severe pain and disability. Disease management historically was based on a "therapeutic pyramid" in which treatment escalated as symptoms worsened. However, the demonstration of early joint damage in patients with rheumatoid arthritis has emphasized the importance of early identification and treatment. Key features in establishing a diagnosis include joint examinations, assessments of extra-articular manifestations, laboratory tests, and radiologic examinations. Care must be taken to rule out other disorders with symptoms that overlap those of rheumatoid arthritis. Treatment of rheumatoid arthritis typically involves disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and low-dose corticosteroids--often used in combination. A new class of therapeutic agents designed to neutralize inflammatory cytokines has added a new dimension to the therapeutic armamentarium against rheumatoid arthritis. Etanercept, a bioengineered soluble receptor fusion protein that blocks tumor necrosis factor activity, is the first compound in this class to be approved for treatment of patients with refractory rheumatoid arthritis. Therapeutic trials indicate that etanercept can reduce disease activity with relatively few drug-related adverse effects, thus helping persons with rheumatoid arthritis return to more normal, healthy lives.
9494993 Rheumatoid arthritis of the forefoot. 1998 Feb Severe and often debilitating involvement of the forefoot is seen frequently in patients with rheumatoid arthritis. The combination of destructive synovitis and weight bearing leads to a spectrum of disorders causing pain, deformity, and eventual loss of function. In addition, advances in total knee and total hip arthroplasty have placed added importance on preserving the ability of the foot and ankle to bear weight and allow functional ambulation. This article reviews the epidemiology, pathophysiology, clinical presentation, physical examination, and treatment of rheumatoid arthritis of the forefoot.
9204258 Management of rheumatoid arthritis. 1997 May There is increasing evidence that reduction of disease activity by disease-modifying drugs alters the disease course of rheumatoid arthritis and that patients benefit from early introduction of disease-modifying antirheumatic drugs. To ensure accurate diagnosis and timely referral, training of medical students and residents in rheumatology and access to a physician experienced in the management of rheumatic diseases is important. Because spontaneous remission is rare, the risk of overtreatment of a few patients is outweighed by the benefits of early treatment for the majority of patients. Also, side effects may be reduced with optimation of titration of disease activity based on standardized, reliable, valid, sensitive, and easily interpretable measures with clear-cut decision rules. A potential solution to the practical problems involving the scoring of patient questionnaires such as the Health Assessment Questionnaire and the Rheumatoid Arthritis Disease Activity index and clinical algorithms such as the Disease Activity Score is the provision of a feedback system similar to a laboratory. To feed back the results of titration of disease activity with the goal of permanently improving health outcomes in an ongoing learning process may be called clinical quality management. From a health care system or political perspective, clinical quality management that demonstrates the commitment of rheumatology toward continuous improvement of rheumatoid arthritis care may become an important activity of rheumatology societies in countries where specialty care is under scrutiny and where specialists are increasingly required to show the benefits of their care.
10652647 Rheumatoid arthritis, disability and the workplace. 1999 Dec Rheumatoid arthritis is a common cause of disability worldwide. The nature of the disability impacts on all areas of life. This chapter focuses on the nature of the disability of rheumatoid arthritis with emphasis on work disability. The various approaches for minimising the disability and rehabilitating those with disability are discussed. The tools for the assessment of disability are described and their strengths and limitations outlined.
9494986 Rheumatoid arthritis of the cervical spine. 1998 Feb Rheumatoid arthritis most often affects the cervical spine, resulting in clinical and radiographic findings. For most patients with rheumatoid arthritis the cervical involvement represents a relatively benign process, but, in a small percentage of these patients, a progressive instability pattern develops that may compromise neural or vascular structures. The rate of neural compromise because of cervical instability ranges from 11% to 58%. The clinical manifestation may be radiculopathy, myelopathy, quadriplegia, and, in extreme instances, sudden death.
9664103 Rheumatoid arthritis in older adults. 1998 Aug Rheumatoid arthritis is a common problem in older adults with varied clinical presentations, which can present a diagnostic challenge. Patients experience a significant functional decline and are placed at increased risk of institutionalization. Multidisciplinary care should focus on all factors contributing to disability, including pain management and depression. Current therapeutic modalities offer an array of choices to the geriatrician. Drug selection should be individualized to reflect each patient's level of disease activity and risk for specific toxicities.