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ID PMID Title PublicationDate abstract
7644784 [Proliferation of large granular lymphocytes in patients with systemic lupus erythematosus 1995 Jun BACKGROUND: Large granular T lymphocytes (LGL) make up a small portion of cellular population in peripheral blood. An abnormal proliferation of LGL is detected together with cytopenic and other autoimmune disorders and is often associated with rheumatoid arthritis. The association with other autoimmune diseases, such as systemic lupus erythematosus, is poorly known. The clinical and immunological profile in five patients with SLE and LGL proliferation is here reported. MATERIALS AND METHODS: A clinical follow-up and prospective phenotypic study of mononuclear cells was conducted in patients with SLE for a period of 24 months. LGL were identified on the basis of their shape and analyzed by flow cytometry as cells coexpressing thymic differentiation antigens (CD3 and CD4, or CD8) and NK cells CD16, CD56 or CD57). RESULTS: Five out of 43 patients with SLE showed recurrent proliferations of LGL (from 2 to 4 per patient) chronologically associated with lupus exacerbations. LGL represented 52 to 78% (mean +/- SD = 56 +/- 8%) from the total of lymphocytes. The phenotype in proliferations was heterogeneous but it was consistent in later relapses in each patient (patient #1 and #2: CD3+CD8-CD4+CD16+CD56+CD57-HLA/D+ patients #3 and #4: CD3+CD8+CD4-CD16+CD56+CD57-HLA/DR+ patient #5: CD3+CD8+CD4- CD16+CD56+CD57-HLA/DR+patient 5:CD3+CD8+CD4-CD16 +/- CD56-CD57+HLA/DR+). These five patients had long term SLE with a greater number of exacerbations and a tendency to develop hemocytopenias, requiring high doses of corticosteroids and even immunosuppressors to control their condition. CONCLUSIONS: Some patients with SLE develop LGL proliferations. The activity, clinical severity and hematological involvement seem to be associated with this immunological disorder, but the pathogenic significance and prognosis of these proliferations are still to be elucidated.
7989549 Comparison of four immunoserologic assays for detection of antibodies to Borrelia burgdorf 1994 Aug In view of the significant sequelae associated with Lyme borreliosis, there is a need for timely and accurate diagnosis of erythema migrans (EM). Although Borrelia burgdorferi can be cultured from biopsies of EM lesions, immunodiagnostic testing is more widely available. Four immunoserologic methods were studied by using the sera of 51 patients with EM lesions that were culture positive for B. burgdorferi. Nineteen patients had single primary lesions, and thirty-two had multiple secondary lesions. At the time of biopsy, 40 patients, 8 with primary lesions and all patients with secondary lesions, were seropositive by an immunoglobulin M (IgM) indirect fluorescent-antibody (IgM IFA) test (Bion Enterprises). Twenty-three patients were seropositive by a whole-cell fluorescence enzyme immunoassay (EIA) (BioWhittaker, Inc.), twenty-two were positive by immunoblotting (ViroStat, Inc.), and one was positive by a P39 recombinant EIA (P39 EIA) (General Biometrics, Inc.). Sera from various patient control groups were tested: rheumatoid arthritis (n = 19), infectious mononucleosis (n = 20), systemic lupus (n = 22), syphilis (n = 13), streptococcal sequelae (n = 20), and healthy subjects (n = 16). None of these sera reacted with the IgM IFA test or P39 EIA. Fifteen reacted with the fluorescence EIA. We conclude that the IgM IFA test is an effective and reliable assay for the diagnosis of EM, particularly for patients with secondary lesions. Immunoblot, fluorescence EIA, and P39 EIA lack the sensitivity to reliably diagnose EM.
12345576 Expanded role for OCs. Question and answer. 1994 Summer
8174459 Drug-induced pulmonary disease. 1994 May Drug-induced disease of any system or organ can be associated with high morbidity and mortality, and it is tremendously costly to the health care of our country. More than 100 medications are known to affect the lungs adversely, including the airways in the form of cough and asthma, the interstitium with interstitial pneumonitis and noncardiac pulmonary edema, and the pleura with pleural effusions. Patients commonly do not even know what medications they are taking, do not bring them to the physician's office for identification, and usually do not relate over-the-counter medications with any problems they have. They assume that all nonprescription drugs are safe. Patients also believe that if they are taking prescription medications at their discretion, meaning on an as-needed basis, then these medications are also not important. This situation stresses just how imperative it is for the physician to take an accurate drug history in all patients seen with unexplained medical situations. Cardiovascular drugs that most commonly produce a pulmonary abnormality are amiodarone, the angiotensin-converting enzyme inhibitors, and beta-blockers. Pulmonary complications will develop in 6% of patients taking amiodarone and 15% taking angiotensin-converting enzyme inhibitors, with the former associated with interstitial pneumonitis that can be fatal and the latter associated with an irritating cough that is not associated with any pathologic or physiologic sequelae of consequence. The beta-blockers can aggravate obstructive lung disease in any patient taking them. Of the antiinflammatory agents, acetylsalicyclic acid can produce several different airway and parenchymal complications, including aggrevation of asthma in up to 5% of patients with asthma, a noncardiac pulmonary edema when levels exceed 40 mg/dl, and a pseudosepsis syndrome. More than 200 products contain aspirin. Low-dose methotrexate is proving to be a problem because granulomatous interstitial pneumonitis develops in 5% of those patients receiving it. This condition occurs most often in patients receiving the drug for rheumatoid arthritis, but it has been reported in a few patients receiving it for refractory asthma. Chemotherapeutic drug-induced lung disease is almost always associated with fever, thus mimicking opportunistic infection, which is the most common cause of pulmonary complications in the immunocompromised host. However, in 10% to 15% of patients, the pulmonary infiltrate is due to an adverse effect from a chemotherapeutic agent. This complication is frequently fatal even when recognized early.(ABSTRACT TRUNCATED AT 400 WORDS)
8157992 Clinical evaluation of a modified ELISA, using photobiotinylated DNA, for the detection of 1994 Mar 29 The measurement of anti-dsDNA antibodies is important for the diagnosis and the follow-up of patients with systemic lupus erythematosus (SLE). For routine detection of anti-dsDNA, the Farr assay and the immunofluorescence technique (IFT) on Crithidia luciliae proved to be very useful. The anti-dsDNA ELISA is not used for routine purposes in our institute since it is flawed by false-positive results due to binding of negatively charged (immune) complexes to the employed precoat (protamine sulphate). Recently, a new anti-dsDNA ELISA has been described in which photobiotinylated dsDNA is coated to streptavidin coated plates. To investigate whether this modified ELISA is more specific than the classical anti-dsDNA ELISA, we tested sera of patients with SLE (n = 51), myasthenia gravis (MG, n = 25), rheumatoid arthritis (RA, n = 25) and Sjögren's syndrome (SS, n = 23) and sera of healthy blood bank donors (BBD, n = 25). In both assays the sera of the SLE patients gave significantly higher values than the sera of healthy blood bank donors. In the classical ELISA, 84% of the sera from patients with RA and 28% of sera of patients with MG were found positive. For the modified assay the figures were 8% and 24%, respectively. This modified ELISA was further studied and clinically evaluated by comparing it with the classical anti-DNA ELISA and two other anti-DNA assays (Farr assay and IFT), using 500 sera sent to our institute for routine anti-DNA determination and sera of an additional 75 healthy blood bank donors. Quantitatively, both ELISAs showed the same high degree of correlation with the IFT. The modified ELISA gave a better correlation with the Farr assay than the classical anti-DNA ELISA. From our data we conclude that the ELISA using photobiotinylated DNA is a more reliable assay than the classical anti-DNA ELISA.
8398047 Diseases and disorders of muscle. 1993 Muscle may suffer from a number of diseases or disorders, some being fatal to humans and animals. Their management or treatment depends on correct diagnosis. Although no single method may be used to identify all diseases, recognition depends on the following diagnostic procedures: (1) history and clinical examination, (2) blood biochemistry, (3) electromyography, (4) muscle biopsy, (5) nuclear magnetic resonance, (6) measurement of muscle cross-sectional area, (7) tests of muscle function, (8) provocation tests, and (9) studies on protein turnover. One or all of these procedures may prove helpful in diagnosis, but even then identification of the disorder may not be possible. Nevertheless, each of these procedures can provide useful information. Among the most common diseases in muscle are the muscular dystrophies, in which the newly identified muscle protein dystrophin is either absent or present at less than normal amounts in both Duchenne and Becker's muscular dystrophy. Although the identification of dystrophin represents a major breakthrough, treatment has not progressed to the experimental stage. Other major diseases of muscle include the inflammatory myopathies and neuropathies. Atrophy and hypertrophy of muscle and the relationship of aging, exercise, and fatigue all add to our understanding of the behavior of normal and abnormal muscle. Some other interesting related diseases and disorders of muscle include myasthenia gravis, muscular dysgenesis, and myclonus. Disorders of energy metabolism include those caused by abnormal glycolysis (Von Gierke's, Pompe's, Cori-Forbes, Andersen's, McArdle's, Hers', and Tauri's diseases) and by the acquired diseases of glycolysis (disorders of mitochondrial oxidation). Still other diseases associated with abnormal energy metabolism include lipid-related disorders (carnitine and carnitine palmitoyl-transferase deficiencies) and myotonic syndromes (myotonia congenita, paramyotonia congenita, hypokalemic and hyperkalemic periodic paralysis, and malignant hyperexia). Diseases of the connective tissues discussed include those of nutritional origin (scurvy, lathyrism, starvation, and protein deficiency), the genetic diseases (dermatosparaxis, Ehlers-Danlos syndrome, osteogenesis imperfecta, Marfan syndrome, homocystinuria, alcaptonuria, epidermolysis bullosa, rheumatoid arthritis in humans, polyarthritis in swine, Aleutian disease of mink, and the several types of systemic lupus erythematosus) and the acquired diseases of connective tissues (abnormal calcification, systemic sclerosis, interstitial lung disease, hepatic fibrosis, and carcinomas of the connective tissues). Several of the diseases of connective tissues may prove to be useful models for determining the relationship of collagen to meat tenderness and its other physical properties. Several other promising models for studying the nutrition-related disorders and the quality-related characteristics of meat are also reviewed.
1573639 Inhibitors of human purine nucleoside phosphorylase. Synthesis and biological activities o 1992 Apr 17 A series of 3-substituted hypoxanthines (6-10, 14-17) and related analogues (22, 23) have been synthesized as inhibitors of purine nucleoside phosphorylase (PNP), which may conceivably act as T-cell-selective immunosuppressive agents with potential utility in autoimmune disorders such as rheumatoid arthritis, in organ transplantations, and in T-cell leukemias. The compounds were evaluated for their PNP activity by a radiochemical assay and also for their cytotoxic effects on a T-lymphoblastoid cell line (MOLT-4). Appropriate substitutions on 3-benzylhypoxanthine (7a) (IC50 in PNP assay, 112 microM; IC50 in MOLT-4 assay, 204.2 microM) increase potency: 8-amino (17a; 42.6, 65.2), 2-hydroxy (9a; 13.4, 28.6), 2-amino (10a; 11.4, 29.1), and 2,8-diamino (16a; 5.0, 11.9). Variation of the 3-aryl substituents of 16a as in 16b-d has thus far failed to further increase potency. Replacement of the 6-oxygen function in 7a with the analoguous nitrogen or sulfur functions, as in 22a and 23a, resulted in little change in activity. Other variations including the increase of the 3-aliphatic chain length as in 6h and 7h (n = 2), the substitution of the phenyl ring with electron-withdrawing groups as in 7e-g, and replacement of the 2-hydrogen with methylthio as in 8a and 14a resulted in decrease of activity. The values for 16a-d represent moderate but significant activities, as compared to the most active inhibitor presently known, 8-amino-9-thienylguanine (1c; 0.17, 0.82). 2,8-Diamino-3-substituted hypoxanthines (16a-d) represent a novel structural type hitherto unreported in the literature, and efficient methodologies for their synthesis were developed in the present studies. The formation of the aminoimidazole moiety occurred through a base-catalyzed 1,5-(O----N)-carbamimidoyl rearrangement (13 to 14, 20 to 16).
1729367 Modification of proinflammatory cytokine production by the antirheumatic agents tenidap an 1992 Jan 15 The cytokines IL-6, IL-1, and TNF play a key role in the pathogenesis of rheumatoid arthritis (RA) and initiate hepatic serum amyloid A (SAA) expression after injury. To provide a possible mechanistic explanation for the previous observation that plasma SAA concentrations decreased during treatment of RA patients with tenidap, but increased during treatment with naproxen, the present study compared the effects of tenidap and naproxen on the two stages of SAA expression: cytokine production by human PBMC and cytokine-stimulated SAA synthesis by human Hep3B hepatoma cells. Tenidap inhibited production of IL-6 greater than TNF greater than IL-1; the effect of naproxen on production of all three cytokines was lesser and least on IL-6. Indeed, an increase in IL-6 production was observed after exposure to naproxen. PBMC beta-2-microglobulin production and total protein synthesis were unaffected at concentrations and times at which effects on cytokine production were observed. Cell density was a significant factor in the extent to which cytokines were stimulated by LPS. Approximately physiologic cell densities, 0.5 to 1 x 10(6) cells/ml, were optimal for stimulation of IL-1-beta and IL-6 production by LPS; however, greater amounts of TNF were produced at lower cell densities. Because neither tenidap nor naproxen inhibited SAA synthesis by cytokine-stimulated Hep3B cells and because they differ most significantly in their effect on IL-6 production, the results support a role for IL-6 in the continued stimulation of SAA production during RA.
8918568 IL-1 receptor antagonist in saliva; characterization in normal saliva and reduced concentr 1996 Nov The characterization of a salivary factor cross-reacting with IL-1 receptor antagonist (IL-1Ra) is described. The apparent molecular weights of two species were 23 kD, consistent with the secreted peptide (sIL-1Ra), and 20 kD, consistent with the intracellular peptide (icIL-1Ra). It had an inhibitory activity on IL-1-stimulated fibroblasts, which is characteristic of IL-1Ra. Its source was the oral mucosa and not the salivary glands. Saliva from patients with SS contained significantly less IL-1Ra than saliva from controls. The decrease was marked in patients with early dental loss but whose xerostomia was still partial. In SS, the salivary IL-1/IL-1Ra imbalance may promote inflammatory lesions in the mouth and impede mucosal cell differentiation.
8796220 Primary Sjögren's syndrome, ulcerative colitis and selective IgA deficiency. 1996 Aug A 24-year-old man with primary Sjögren's syndrome presented with xerophthalmia, xerostomia, and marked parotid swelling. He had a previous history of selective IgA deficiency and ulcerative colitis treated with sulphasalazine. Immunosuppression and withdrawal of sulphasalazine resulted in rapid resolution of the parotitis and disappearance of autoantibodies. A possible role for sulphasalazine in the induction of autoimmunity in this case is discussed.
8551269 Large-scale study suggests no direct link between human herpesvirus-6 and primary Sjögren 1995 Nov The aim of this study was to evaluate the role of human herpesvirus-6 (HHV-6) in the development of primary Sjögren's syndrome (PSS). Serum HHV-6 antibody levels, as measured by immunofluorescence assay (IFA) and the prevalence of HHV-6 DNA in peripheral blood mononuclear cells (PBMCs) determined by polymerase chain reaction (PCR), were studied in 49 PSS patients and 50 control subjects, all in-patients in the University Hospital Internal Medicine ward, Limoges, France. In addition, portions of labial salivary gland were obtained from 34 patients and 15 controls, the presence of viral DNA being detected by the same PCR technique. The results were then compared with clinical observations of systemic disease manifestations in patients and a histological study of salivary gland involvement. No significant difference in HHV-6 seroprevalence was found between control subjects (50.0%) and patients (63.3%) nor was there any statistically significant difference between patient and control groups for total viral DNA in PBMCs (22.4%, 12.0%) and salivary glands (8.8%, 6.6%). Analysis of clinical and histological data revealed no detectable correlation between disease severity and viral involvement. Tests for HHV-6A and HHV-6B proved positive in patient and control groups, HHV-6B being the most frequently encountered type in both groups. In conclusion, the results of this large-scale trial does not confirm the suspected direct role of HHV-6 in the etiology of PSS.
7579463 Heterogeneity of neutrophil antibodies in patients with primary Sjögren's syndrome. 1995 Nov 1 Our aims were to determine the prevalence of neutrophil antibodies in patients with primary Sjögren's syndrome (pSS), identify their target antigen(s), and evaluate their functional significance. Neutrophil antibodies were detected using an indirect immunofluorescence (IIIF) test and an enzyme-linked immunosorbent assay (ELISA), using recombinant human Fc-gamma receptor (Fc gamma RIIIb) as a capture agent. Luminol-dependent chemiluminescence was then measured by an established technique. Antibodies to neutrophils were detected in 30 of 66 patients (45%) and categorized on the basis of positivity for the two assays: IIF+/ELISA+ (group A: five patients), IIF+/ELISA- (group B: five patients), and IFF-/ELISA+ (group C: 20 patients). All positive sera contained antibodies directed to the neutrophil specific Fc gamma RIIIb, and none of them bound to NAnull neutrophils. The titer of neutrophil-reactive antibodies (groups A and B) showed no correlation with the neutrophil count, but these autoantibodies did reduce the cell ability to generate a respiratory burst. Thus, neutrophil antibodies are common in patients with pSS. Their main target appears to be Fc gamma RIII, and this may partly account for the dysfunction in Fc gamma R-mediated clearance by the reticuloendothelial system reported in these patients.
8191396 High-titer antinuclear antibodies, anti-SSA/Ro antibodies and anti-nuclear RNP antibodies 1994 Feb The clinical significance of high-titer antinuclear antibodies (ANA) and autoantibodies to cellular antigens such as SSA/Ro and nuclear RNP (nRNP) antigens in idiopathic thrombocytopenic purpura (ITP) was examined in a prospective evaluation of 66 adult patients with chronic ITP. ANA were positive in 29 (44%) of 66 patients with chronic ITP. The titers of ANA were high (1:160 or higher) in 14 of 29 ANA-positive patients. Furthermore, 10 of 66 patients had precipitating antibodies to nuclear antigens; seven patients had anti-SSA/Ro antibodies and the other three had anti-nRNP antibodies. None of high-titer ANA- or precipitating antibody-positive patients developed systemic lupus erythematosus (SLE) throughout the follow-up period of 3 years. In addition, we investigated retrospectively precipitating antibodies in stocked sera from 8 patients. These patients had already precipitating antibodies average of 7.7 years before. None of 8 patients developed SLE or Sjogren's syndrome (SS). These data demonstrate that high-titer ANA and antibodies to SSA/Ro or nRNP antigens are often found in patients with ITP, and indicate that the detection of high-titer ANA or the existence of antibodies to SSA/Ro or nRNP antigens by itself is not enough to identify those patients with ITP who are at risk of developing SLE or SS.
1348259 Sulfasalazine-induced fulminant hepatic failure. 1992 Mar We report two cases of massive hepatic necrosis associated with sulfasalazine. Both patients had underlying inflammatory bowel disease. One of the patients had a history of an ill-defined autoimmune disorder (Sjögren's syndrome). Symptoms and signs of a generalized hypersensitivity reaction were present in both patients. One patient died of a subarachnoid hemorrhage while awaiting transplant, the second died 2 weeks after transplant from disseminated aspergillosis. These two cases remind us of one of the potential hazards of sulfasalazine at a time when alternative therapies are now available.
8974073 Circulating antibodies against neonatal cardiac muscarinic acetylcholine receptor in patie 1996 Oct Isolated congenital heart block may be associated with Primary Sjögren's Syndrome. In this work we demonstrated that IgG present in the sera of patients with Primary Sjögren's Syndrome (PSS) could bind and activate muscarinic acetylcholine receptors of rat neonatal atria. These antibodies were able to inhibit in a irreversible manner the binding of 3H-QNB to muscarinic cholinergic receptors of purified rat atria membranes. Moreover, IgG from PSS individuals could modify biological effects mediated by muscarinic cholinoceptors activation, i.e. decrease contractility and cAMP and increase phosphoinositide turnover and cGMP. Atropine blocked all of these effects and carbachol mimicked them; confirming muscarinic cholinergic receptors-mediated PSS IgG action. Neither binding nor biological effect were obtained using adult instead of neonatal rat atria. IgG from sera of normal women were not effective in the studied system. The prevalence of cholinergic antibody was 100% in PSS and was independent of Ro/SS-A and La/SS-B antibodies. It could be concluded that antibody against muscarinic cholinergic receptors may be another serum factor to be considered in the pathophysiology of the development of congenital heart block.
7564846 Nodal inclusion cysts of the parotid gland and parapharyngeal space: a discussion of lymph 1995 Oct The purpose of this report is to examine the computed tomography scans, magnetic resonance images, and pathologic findings in 44 patients, 42 of whom had inclusion-type cysts of the parotid and parapharyngeal space of varying etiologies. Two additional cases of cystic changes in the benign lymphoepithelial lesion (BLEL) of Sjögren's syndrome are highlighted here, since they had unusually large cystic components mimicking acquired immunodeficiency syndrome-related parotid cysts (ARPCs). A retrospective examination identified 18 ARPCs, 3 lymphoepithelial cysts (LECs), 13 cystic Warthin's tumors, 8 branchial cysts, and 2 cases of cysts in patients with Sjögren's syndrome (BLEL), all of whom had imaging studies and pathologic confirmation. There were 30 men and 14 women with an age range of 25 to 72 years (median, 46.82 years). Any similarities in the imaging appearances were noted, as were any differences in pathologic detail. On imaging, only the cystic Warthin's tumors had any focal wall nodularity; the other cysts had smooth walls. When multiple parotid cysts were present, the distinguishing feature between ARPCs and cysts in BLEL (and some cystic Warthin's tumors) was the presence of diffuse cervical adenopathy in patients with ARPCs. Imaging usually could not differentiate between a solitary parotid LEC, a branchial cyst, and some cystic Warthin's tumors. Extraparotid lesions were either branchial cysts or cystic Warthin's tumors. Physicians should be aware of the variety of different inclusion-type cysts that may occur in the parotid gland and parapharyngeal space, all of which may have similar imaging appearances. Although imaging clearly identifies these cysts and may suggest a specific diagnosis, it must always be remembered that the precise diagnosis remains in the province of the pathologist.
8536103 Analysis of transforming growth factor beta and other cytokines in autoimmune exocrinopath 1995 Sep Cytokines play a major role in tissue destruction caused by autoimmune dysregulation. In Sjögren's syndrome (SS) patients, salivary glands are the target organs for autoimmune tissue damage. In the present study, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to look for cytokine mRNA expressed in SS salivary glands. Focus score was used to determine the severity of the lesions. Cytokine production in supernatants of the salivary gland cell culture was measured by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical staining was used to identify the local presence of transforming growth factor beta (TGF-beta). Interleukin (IL)-2, IL-6, and IL-10 mRNA were expressed in moderate to severe SS salivary gland lesions. TGF-beta mRNA was constitutively expressed in normal and SS salivary glands. In SS salivary gland cell cultures, IL-6 and IL-10 proteins were produced. TGF-beta production was reduced in high focus score SS glands. Normal and minimally involved SS salivary gland ductal epithelium and acinar cells were found to produce TGF-beta by immunostaining. In conclusion, an excess production of IL-2, IL-6, and IL-10 and a reduced production of the immunosuppressive cytokine, TGF-beta, may be responsible for the progression of the salivary gland lesion in SS. Specific immunotherapy can now be designed based on mechanisms to correct this cytokine imbalance and benefit patients with autoimmune diseases, such as SS.
7699659 An association of fibromyalgia with primary Sjögren's syndrome: a prospective study of 72 1995 Jan OBJECTIVE: Fibromyalgia patients often describe the presence of dry eyes and dry mouth. Conversely there is an increasing recognition that many patients with Sjögren's syndrome (SS) have fibromyalgia (FM). We decided to investigate this association. METHODS: Seventy-two patients with FM were screened with a Schirmer's test. All patients with an abnormal test had a minor salivary gland biopsy. RESULTS: Thirty-eight percent (n = 28) had a Schirmer's test of < 15 mm wetting at 5 minutes, however sicca symptoms were noted in only 19% of patients. Salivary gland biopsy in these 28 patients showed a focus score of > or = 1 in 5; a positive antinuclear antibody test (ANA) was found in 4, a positive rheumatoid factor in 3 and anti-SSA SSB antibodies in 2. Another 8 patients had abnormal salivary gland lymphocytic foci, but there were < 50 cells or the density was < 1 focus/4 mm2; all 8 of these patients had a positive ANA. None of these patients have developed systemic features of SS over a 6 year period of followup. CONCLUSION: There is a subgroup of patients presenting with FM who, on further testing, have findings consistent with primary SS. The prevalence of this association was 6.9% for probable SS and 11% for possible SS. These figures are probably an overestimation due to tertiary center referral bias. The etiologic and management implications of these observations are unclear.
7950838 Early detection of lymphomas in Sjögren's syndrome by in situ hybridisation for kappa and 1994 Jul Sjögren's syndrome (SS) is an autoimmune disease characterised by a generalised lymphoproliferation. Patients have an increased risk of developing lymphomas which are usually of the type associated with mucosa-associated lymphoid tissue (MALT). Histological examination of the minor salivary glands of the lower lip is a common and useful diagnostic test for SS but has not been able to provide information with regard to potential malignant change. In this study, a sensitive in situ hybridisation technique for the detection of kappa and lambda immunoglobulin light-chain mRNA was applied to labial salivary glands of 14 patients with SS. 7 cases showed light chain restriction, in 5 cases this was kappa(kappa:lambda ratio > 8.0) and in 2 it was lambda(kappa:lambda ratio < 0.6). Of these 7, 5 developed lymphomas--4 were low grade lymphomas of MALT type and the fifth patient died of disseminated lymphoma. The finding of light chain restriction in lip minor salivary glands is strong evidence of a monoclonal population of B-cells at this site. It is concluded that in patients with SS who develop lymphomas, dissemination of malignant cells may result in detectable disease in the minor salivary glands. Determination of kappa:lambda ratios in labial minor salivary glands may thus provide important prognostic information.
8251415 High incidence of lymphoid infiltration on labial salivary gland biopsy in non-Hodgkin's l 1993 Sep Sjögren's syndrome (SS) is characterized by an increased risk of developing a non-Hodgkin's lymphoma (NHL). We performed labial salivary gland biopsy (LSGB) in 103 patients with untreated NHL, negative for human immunodeficiency virus. Median age was 58 years (range 21-79) and M/F 1.3. Using the Working Formulation, 37 patients had low-grade NHL and 66 had intermediate- or high-grade NHL. Dense lymphocytic infiltration (positive focus score 3 or 4) was found in 28 patients. 10 (35%) of these 28 patients fulfilled criteria for possible SS. 15/28 patients had an identical monotypic infiltrate on LSGB and NHL tissue (including two of the 10 patients with criteria for SS). The significance of the lymphoid infiltrate of LSGB was unknown in the five remaining patients with positive focus score. Significant correlations were found between positive focus score and presence of two or more extranodal sites of disease (P = 0.02), impaired performance status (P = 0.004), splenomegaly (P = 0.05), increased gammaglobulin level (P = 0.03), and beta 2 microglobulin (P = 0.004). Considering intermediate- or high-grade NHL, we found significant correlation between positive focus score and unfavourable prognosis according to the two Dana Farber Cancer Institute indexes (P < 0.04), to the LNH-84 index (P = 0.05), and to the international index (P = 0.003). In conclusion, systematic evaluation of LSGB in 103 patients with NHL found lymphoid infiltration in 28% of them, but possible SS could be considered in only 10%. This lymphoid infiltration, though not correlated with any particular histological subtypes, was associated with unfavourable clinical prognostic factors, especially in intermediate- or high-grade NHL.