Association between early onset and organ manifestations of systemic lupus erythematosus (SLE) and a down-regulating promoter polymorphism in the MBL2 gene.

The serum concentration of mannose-binding lectin (MBL) is genetically determined by a series of allelic polymorphisms in the MBL2 gene. Since several polymorphisms of the MBL2 gene have been suggested to be risk locus for systemic lupus erythematosus (SLE), we investigated MBL2 polymorphisms in 315 SLE patients from Hungary and 182 geographically matched healthy controls. Within the group of patients, we found that homozygotes for an MBL2 down-regulating promoter polymorphism at position -221 (YA to XA) (rs7096206) were significantly (p=0.017) younger at diagnosis than the other patients. The frequency of juvenile-onset SLE (

Investigation of cytokine (tumor necrosis factor-alpha, interleukin-6, interleukin-10) concentrations in the cerebrospinal fluid of female patients with multiple sclerosis and systemic lupus erythematosus.

Humoral immune response seems to play a role in the pathogenesis of multiple sclerosis (MS) and in the central nervous system (CNS) complications of systemic lupus erythematosus (SLE). The aim of the present study was to compare the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 in the cerebrospinal fluid of female patients with several forms of MS (50 patients), and in female patients with several types of CNS complications in SLE (50 patients). Samples were investigated using an enzyme-linked immunosorbent assay technique. Involvement of CNS in SLE patients seems to be characterized with elevated concentrations of all three cytokines in CNS and intrathecal synthesis of IL-6. In MS patients, an intrathecal synthesis of TNF-alpha (relapsing-remitting form) and IL-6 (primary progressive form) were observed. Clinical forms of MS seem to be immunologically heterogeneous. The activation of cytokine network was observed in SLE patients with CNS complications, independent of the pathological process. Similarities between SLE and MS patients with the primary progressive form of the disease were demonstrated concerning the intrathecal synthesis of IL-6. Only MS patients with the relapsing-remitting clinical form showed intrathecal TNF-alpha synthesis.

Concentration of soluble adhesion molecules (sVCAM-1, sICAM-1 and sL-selectin) in the cerebrospinal fluid and serum of patients with multiple sclerosis and systemic lupus erythematosus with central nervous involvement.

OBJECTIVES: The aim of the present study was to investigate the role of soluble adhesion molecules in the pathogenesis of multiple sclerosis (MS) and systemic lupus erythematosus (SLE) with demyelinating syndrome. METHODS: Paired cerebrospinal fluid (CSF) and serum samples were analysed by an ELISA method to determine the concentrations of sVCAM-1, sICAM-1 and sL-selectin. Intrathecal syntheses of the adhesion molecules were calculated. RESULTS: Elevated serum and CSF concentrations of sVCAM-1 were present in all patient groups. Intrathecal synthesis of sVCAM-1 was present in the relapsing-remitting and secondary progressive forms of MS. Intrathecal synthesis of sICAM-1 was observed in all clinical forms of MS. MS patients with progressive forms of the disease and SLE patients were characterised by intrathecal synthesis of sL-selectin. CONCLUSIONS: The data presented suggest that (1) blood-brain barrier damage can be assumed both in systemic disease and organ-specific disease (sVCAM-1), (2) clinical forms of MS differ from each other in respect to concentrations of adhesion molecules and (3) similar immunological events in the central nervous system of SLE patients with demyelinating syndrome and progressive forms of MS can be assumed (sL-selectin).

High levels of antibodies against Clq are associated with disease activity and nephritis but not with other organ manifestations in SLE patients.

OBJECTIVE: Serum concentration of antibodies to C1q (C1qAb) has been reported to be elevated in a high percentage of patients with systemic lupus erythematosus (SLE). The associations of high C1qAb levels with different clinical manifestations and the activity of the disease, however, are not definitely understood. METHODS: We measured the levels of IgG type C1qAb in the sera of 137 patients with SLE using an ELISA method. RESULTS: Serum concentrations of C1qAb were found to be higher (p < 0.0001) in SLE patients than in healthy controls. High titer (> 66 AU/ml) C1qAb was found in 40/137 (29.2%) SLE patients, and 4/192 (2.1%) healthy controls (p < 0.0001). A strong negative correlation (R = -0.4, p < 0.0001) between the age of the patients and the C1qAb titers could be detected. C1qAb levels in clinically active SLE patients significantly (p < 0.0001) exceeded those measured in the sera of patients in the inactive stage of the disease. A significant positive correlation was detected between C1qAb levels and the laboratory activity markers (anti-DNA, low C3 level) of the disease. We found a significant negative correlation between levels of C1qAb and a negative acute phase protein, alpha2-HS-glycoprotein. Renal involvement was present in 11/40 (27.5%) and 11/97 (11%) of the patients with high and low titers of C1qAb, respectively (p = 0.038). The prevalence of other organ manifestations was, however, the same in the patients with or without high titer C1qAb. CONCLUSION: These findings indicate that C1qAb measurement is a useful method for detecting the activity of SLE and predicting renal manifestations, but not other organ involvement in the disease.

Increased interferon-gamma (IFN-gamma), IL-10 and decreased IL-4 mRNA expression in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE).

Cytokines are important regulators of lymphocyte function in SLE. However, the profile of Th1 and Th2 cytokines produced by circulating lymphocytes in human SLE has not been clearly elucidated. The aim of the present study was to characterize the gene expressions of the Th1-type cytokine IFN-gamma, and the Th2-type cytokines IL-10 and IL-4 in PBMC of 15 patients with SLE and 10 healthy individuals by a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Our results showed that expression of IFN-gamma (P = 0.0004) and IL-10 (P = 0.002) transcripts were significantly increased in PBMC of patients with SLE compared with healthy controls. By contrast, expression of IL-4 transcripts in PBMC of patients with SLE was significantly decreased compared with the healthy controls (P = 0.0008). Primary sources of IL-10 were B cells and monocytes, with variable contribution of T cells as detected in various fractions of PBMC of patients with SLE (P = 0.049). These findings support the hypothesis that the enhanced production of IFN-gamma by mononuclear cells may trigger inflammatory responses, together with the enhanced production of IL-10 resulting in autoantibody production by B cells in human SLE.

Soluble L-selectin levels in serum and cerebrospinal fluid in patients with multiple sclerosis and systemic lupus erythematosus.

Soluble L-selectin (sL-selectin) concentrations were measured in paired samples of serum and cerebrospinal fluid by an ELISA method. Patients with several forms of multiple sclerosis (MS) and systemic lupus erythematosus with central nervous system involvement (SLE-CNS) were investigated. Elevated CSF sL-selectin concentrations were found in patients with SLE-CNS (7.62 +/- 3.31 ng/ml) and with relapsing-remitting form of MS (6.99 +/- 4.72 ng/ml) compared to the control group (4.00 +/- 0.95 ng/ml). The data presented suggest some similarities between inflammatory/immunological events in the central nervous system in patients with SLE-CNS and relapsing-remitting form of MS. Immunological heterogeneity in MS is suspected.

[Splenic rupture: a rare complication of colonoscopy]. / Kolonoszkópia ritka szövódménye: a lépruptura.

Splenic rupture due to colonoscopy is very rare. Only a few cases have been reported previously in the English literature. Authors present their own case and they call attention to the mechanism of this complication. They conclude consequences from the literature.

A study of increased levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) in the cerebrospinal fluid of patients with multiple sclerosis and systemic lupus erythematosus.

The concentration of soluble vascular cell adhesion molecules (sVCAM-1) of serum and cerebrospinal fluid (CSF) was measured in clinically selected multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients, using an ELISA assay. The mean sVCAM-1 concentration in the serum of SLE patients was higher than normal. The mean CSF sVCAM-1 concentration was increased in the MS as in the SLE group. On analysis, the data suggests that there are some similarities in the immunological effects of these two different diseases of the central nervous system. A longitudinal analysis of the CSF is requested.

[Clinical significance of antiphospholipid autoantibodies in lupus erythematosus]. / Az antifoszfolipid autoantitestek klinikai jelentösége szisztémás lupus erythematosusban.

The authors have determined the prevalence of antibodies of cofactor dependent anticardiolipin and beta 2-glycoprotein I and lupus anticoagulant and the frequency of false positive VDRL test in systemic lupus erythematosus. The aim of this retrospective study was to assess the presence of these antibodies and symptoms of antiphospholipid syndrome. The serum samples were examined by modified ELISA method for detecting of cofactor dependent anticardiolipin. The antibodies to beta 2-glycoprotein I were examined by ELISA. The lupus anticoagulant and VDRL test were performed by routine laboratory method. The authors have found that 19 of 58 patients with systemic lupus erythematosus had cofactor dependent anticardiolipin, 10 patients had antibodies to beta 2-glycoprotein I and 4 patients had positive VDRL test. 5 of 34 plasma samples were lupus anticoagulant positive. 19 patients with systemic lupus erythematosus had 14 neuropsychiatric disorders, 9 cardiovascular diseases, 7 thrombocytopenia, 6 histories of recurrent abortion and fetal loss, 5 livedo reticularis and 3 thromboembolic events in all of them had detected antibodies to cofactor dependent anticardiolipin, while these complications were diagnosed in 39 anticardiolipin negative patients much more rarely. The results of this retrospective study suggest that significant association exists between the presence of cofactor dependent anticardiolipin and symptoms of antiphospholipid syndrome in systemic lupus erythematosus.

[Systemic lupus erythematosus and pregnancy (effect of pre-conception hematologic disorders on fetal outcome)]. / Szisztémás lupus erythematosus és terhesség (prekoncepcionális haematológiai rendellenességek hatása a magzati eredményekre).

The aim of the study was to determine the fetal and neonatal outcomes of pregnancies conceived during the inactive phase of systemic lupus erythematosus (SLE). Fetal and neonatal outcomes in 75 pregnancies of 33 patients with SLE were analyzed. In 19 patients (57.6%) the SLE also had hematological autoimmune presentations prior to gestation, such as anemia, thrombopenia, garnulocytopenia, and antiphospholipid antibody and/or lupus anticoagulant (APA). Out of 75 pregnancies, 19 elective terminations were carried out because the disease was active or for non-medical reasons. The adverse fetal outcomes of those 56 pregnancies which occurred during the inactive phase were compared with those of the control patients. In SLE, the rates of spontaneous abortions (46.4%) and newborns with low (< 2500 gr) birthweight (36.7%) were found to increase roughly three times that of the controls and the perinatal fetal loss (16.7%) also increased significantly as compared with the control group (28.5 per thousand). APA noted at any time before pregnancy increased the low birthweight rate (75%) six fold and the perinatal loss (33.3%) more than ten fold but did not affect the rate of spontaneous abortions. Any kind of hemocytopenias without APA, noted before pregnancy did not worsen the fetal outcome in SLE. Neonatal lupus was diagnosed in 2 out of the 30 newborns. Our results suggest that among the hematologic manifestations of SLE presenting before pregnancy, APA can predict the high risks of low birthweight and perinatal fetal loss as opposed to hemocytopenias.

[Diagnostic value of the determination of serum alpha2-HS-glycoprotein]. / A szérum alpha 2-HS-glycoprotein meghatározások diagnosztikus értékéröl.

Opsonic glycoprotein, alpha 2-HS-glycoprotein concentration was studied in the serum of 753 patients with various hematological, malignant, immunological, metabolic, endocrine and liver diseases and 68 healthy controls. Decreased serum alpha 2-HS-glycoprotein levels were detected in patients with acute leukemias, chronic granulocyte and myelomonocyte leukemias, lymphomas, myelofibrosis, multiple myeloma, metastatizing solid tumors, systemic lupus erythematosus, rheumatoid arthritis, acute alcoholic hepatitis, fatty liver, chronic active hepatitis, liver cirrhosis, acute and chronic pancreatitis, and Crohn's disease. Elevated levels were measured in patients with B and NANB/C hepatitis. Further decreased levels were observed in some groups with secondary infections. Serum alpha 2-HS-glycoprotein levels are affected by many factors, influencing the synthesis and elimination of the protein. The detection of serum alpha 2-HS-glycoprotein concentration has no specific diagnostic value as a marker for tumors or other diseases, however, its determination can be useful for the assessment of a non-specific regulator of the host defence.

[Effect of estrogen on the blast transformation of lymphocytes and interleukin-2 production in lupus erythematosus]. / Oestrogen hatása a lymphocyta blastos transformatióra és az interleukin-2 termelésre systemás lupus erythematosusban.

The mitogenic response of peripheral lymphocytes was investigated in 12 patients with systemic lupus erythematosus and in healthy female volunteers who were on 11 and without 9 contraceptive pills. The effect of estrogen (ethinyl-estradiol 10(-5)-10(-6)-10(-7)M) was studied on Phytohaemagglutinin and Pokeweed mitogen induced blastogenic transformation and interleukin-2 production of peripheral lymphocytes in vitro. We observed a significantly depressed Phytohaemagglutinin induced lymphoblastic transformation both in patients and women taking oral contraceptive in presence of 10(-5)M estrogen as compared to normal controls. However there was no significant alteration neither in the response of lymphocyte nor in the production of interleukin-2 using of Pokeweed mitogen. The stimulataneous inhibition of the interleukin-2 production proved to be moderate. Marked significant correlation (r greater than = 0.8) vas detected between lymphoblastic transformation and interleukin-2 production in healthy females. Correlation coefficient measured in females taking oral contraceptive (r less than = 0.64) and patients with systemic lupus erythematosus (r less than = 0.34) suggest that in these groups the inhibition of lymphoblastic transformation is due to the inhibition effect of estrogen on the interleukin-2 production.

PIP: 12 patients with systemic lupus erythematosus (SLE) (8 in the active stage) with an average age of 26 years (17-54) and 20 healthy control subjects (9 were aged 18-49 years and 11 were oral contraceptives [OC] users aged 17-44) were studied to assess the inhibiting effect of estrogen in vitro on phytohemagglutinin (PHA) and Pokeweed (PWM) mitogen induced blast transformation of lymphocytes (lymphoblastic transformation=LBT) gained from periphral blood and simultaneous interleukin-2 (IL-2) production. 8 women were taking Anteovin, 2 Ovidon, and 1 Rigevidon. The average duration of OC use was 5.2 years. 1 SLE patient did not need immunosuppressive treatment, 3 patients received corticosteroid maintenance therapy, and 4 patients were also taking 50 mg of Imuran. In 4 active SLE patients the tests were done before raising the dose of immunosuppressive drugs, and in the case of 2 other patients the administration of 75 mg and 25 mg/die Prednisolone was necessary in addition to 50 mg and 100 mg/die Imuran. LBT decreased significantly in patients and OC users. The LBT values induced by PWM were similar but not significant. The IL-2 production induced by PHA decreased in all 3 groups but not significantly. I1-2 production was 6 E/ml in patients, 5 E/ml in OC users, and 11.5 E/ml in nonusers, but the differences did not prove significant because of wide individual fluctuations. The amount of IL-2 produced by lymphocytes at PWM stimulation was almost the same in all 3 groups with or without estrogen. There was a positive, significant relationship between the extent of LBT and the amount of IL-2 produced in the healthy group of nonusers, it was less solid in the OC users, and in the SLE group trhe low correlation coefficient of .34 suggested the reduction of IL-2 through the inhibition of LBT.

Serum alpha 2-HS glycoprotein concentration in patients with hematological malignancies. A follow-up study.

We observed significantly reduced serum alpha 2-HS glycoprotein concentrations in patients with acute lymphocytic, acute nonlymphocytic, chronic granulocytic and chronic myelomonocytic leukemias, Hodgkin's and non-Hodgkin's lymphomas, myelofibrosis, and multiple myeloma, but not in patients with chronic lymphocytic leukemia and polycythemia vera, as compared with healthy controls. We followed the serum level of the protein for 18 months. Patients with infectious complications, those receiving cytostatic treatment, and those in the preterminal period had further reduced serum alpha 2-HS glycoprotein levels. The reduction of serum alpha 2-HS glycoprotein concentration was primarily due to decreased production caused by infiltration of the liver, a hepatotoxic effect of cytostatic treatment, and, to a lesser degree, to increased consumption. We found statistically significant negative correlations between serum alpha 2-HS glycoprotein concentration and erythrocyte sedimentation rate, serum aspartate aminotransferase and alkaline phosphatase activities, and IgG and IgM concentrations. The determination of the alpha 2-HS glycoprotein concentration is useful for the assessment and follow-up of the clinical status and therapy of patients with hematological malignancies and also has prognostic significance.

[The role of the central nervous system in lupus erythematosus]. / A központi idegrendszer részvétele systemás lupus erythematosusban.

Central nervous system involvement of systemic lupus erythematosus was observed in 34 (36%) of the 94 patients studied between 1970-1990. A review of the diagnostic methods and therapy for central nervous system lupus is presented. The diagnosis of primary cerebral lupus was based on the history, physical examination and on the results of the cerebrospinal fluid analysis, CT-scan and EEG. Intractable headache (22/34), behavioural abnormalities (18/34), cranial neuropathy (16/34) occurred most frequently among neuropsychiatric symptoms. Immunoglobulin analysis of the cerebrospinal fluid proved to be the most sensitive method for detecting clinical activity (in 20/23). Central nervous system involvement was suggested by conventional serological test to a lesser degree. Alterations on CT scan and EEG were found in 17/27 and 14/26 of cases, respectively. IgM, IgA, and IgG indexes (indicators of intratechal immunglobulin synthesis) decreased when the central nervous system events subsided after successful treatment but the CT abnormalities (e. g. atrophy) were not altered.

The effect of the alpha 2-HS-glycoprotein on the mitogen-induced lymphoblastic transformation and IL-2 production.

Authors investigated the in vitro effect of alpha 2-HS-glycoprotein on the lymphoblastic transformation and interleukin-2 production. The observations were made on the peripheral blood lymphocytes of healthy persons, on those of women taking oral contraceptives and on those of patients with systemic lupus erythematosus. The alpha 2-HS-glycoprotein inhibited the mitogen responses both in physiologic and in the halved concentrations. The inhibition of the interleukin-2 production seemed less remarkable.

PIP: Whether blast transformation of human lymphocytes from healthy volunteers, women taking oral contraceptives, and women with systemic lupus erythematosus (SLE) would be affected by alpha2-HS-glycoprotein (A2HSGP) was explored by incubating lymphocytes stimulated by phytohemagglutinin or pokeweed mitogen with or without the glycoprotein. A2HSGP did indeed inhibit blast transformation in these cell populations. Release of the peptide interleukin-2 into the culture medium was also inhibited to a lesser extent, slightly more so in cells from healthy persons, and slightly less so in women with SLE. The mechanism and biological significance of this observation is unexplained.

Correlations between serum alpha 2-HS-glycoprotein concentration and conventional laboratory parameters in systemic lupus erythematosus.

Serum alpha 2HS-glycoprotein (A2HSG) concentrations of 63 patients with systemic lupus erythematosus (SLE) were determined, and found to be significantly low compared to those of 59 healthy blood donors. The diminution of serum A2HSG concentration was proportional to the degree of activity of SLE, and was not influenced by secondary infections. There was a statistically significant positive correlation between serum A2HSG and the C3 complement component levels. A negative correlation between serum A2HSG and IgG, IgA concentration and anti-DNA activity was observed. Serum A2HSG was significantly low in cases of positive for the following laboratory parameters: anti-nuclear antibodies, circulating immune complexes and LE cell phenomenon. We found no correlation between serum IgM concentration, cryoglobulins, latex agglutination and serum A2HSG levels. The unusually good negative correlation between A2HSG pathogenetical role of this glycoprotein in SLE. The determination of A2HSG concentration may be of clinical importance in SLE.

[Systemic lupus erythematosus and pregnancy]. / Systemás lupus erythematosus és a terhesség.

The authors report on the successful outcome of pregnancy of a young woman with systemic lupus erythematosus. Her disease presented with severe renal involvement. The delivery was followed by lasting, complete remission. Even at the time of the report both the mother and her child are in a good health. On the occasion of this case-history the authors attempts, to summarize the present knowledge of pregnancy in systemic lupus erythematosus.

[Effect of female sex hormones on blastic transformation of lymphocytes in systemic lupus erythematosus and in healthy women]. / A nöl nemi hormonok hatása a lymphocyta blastos transformatióra systhemás lupus erythematosusban és egészséges nökben.

PIP: The susceptibility of women to autoimmune diseases is well-documented, of which systemic lupus erythematosus (SLE) is especially important. The use of oral contraceptives often activate SLE from a quiescent condition. The inductive effect of estrogen has been shown in animal studies indicating that female hormones can trigger autoimmune reaction. The effect of ethinyl estradiol, an estrogen (E), and d-norgestrel, a progesterone (P), on the mitogenic response of peripheral lymphocytes, and particularly on phytohemagglutinin (PHA)- and concanavalin-A (Con-A)-induced blastic transformation of lymphocytes (LBT) was studied in vitro. 25 patients with SLE and 27 healthy controls participated in the study. SLE was inactive in 16 patients, 7 took corticosteroids, and 3 also received 50 mg/day Imuran. 13 patients and 10 controls took contraceptives (Bisecurin, Infecundin, Ovidon, Rigevidon). The LBT value fell significantly in patients with active SLE, in contraceptive users, and the value was significantly lower in inactive patients than in those not using contraceptives. E and P separately or together significantly reduced LBT values. Contraceptives containing P only can be prescribed for women suffering from SLE, as its role in inducing the disease compared to E is negligible.^ieng

[Determination of plasma fibronectin in myeloproliferative and lymphoproliferative diseases and other malignancies]. / Bestimmung der Plasmafibronektin-Konzentrationen in myeloproliferativen und lymphoproliferativen Erkrankungen und anderen Malignomen.

Plasma fibronectin concentration was determined by electroimmunodiffusion and laser nephelometry in 40 healthy persons and 321 patients with myelo- and lymphoproliferative diseases and other malignancies. Decreased fibronectin concentrations were found in patients with leukemia, Hodgkin's and non-Hodgkin's lymphomas, myelofibrosis, polycythaemia rubra vera and angioimmunoblastic lymphadenopathy. Elevated fibronectin level was detected in patients with multiple myeloma. In patients with cancer of the lung, stomach and colon, fibronectin level was found in the normal range. Decreased fibronectin concentration was observed in patients with cancer of the breast and prostate. Lower plasma fibronectin concentrations were detected in all groups of patients with infectious septical complications as compared to the patients without infections.