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J Antonen

Publications and source records attributed to J Antonen.

At least 19 recordsLinked to original sources
PubMed2005

Th2 cytokine genotypes are associated with a milder form of primary Sjogren's syndrome.

BACKGROUND: Immunohistological studies on salivary and lacrimal glands have yielded conflicting results on the Th1/Th2 balance in primary Sjögren's syndrome (pSS). OBJECTIVE: To establish whether pSS is a Th1 or Th2 directed autoimmune disease by analysing the polymorphism of the genes encoding for cytokines involved in the regulation of Th1/Th2 differentiation. METHODS: The polymorphisms of the genes encoding for interleukin 4 (IL4) -590 C/T, interleukin 13 (IL13) +2044 G/A, and interferon gamma (IFNG) +874 T/A were analysed in 63 white Finnish patients with pSS (61 female, two male) and in 63 healthy controls. The clinical and immunological data on the pSS patients were analysed in relation to these cytokine gene polymorphisms. RESULTS: There were no significant differences in the genotype or allele frequencies of IL4 -590, IL13 +2044, or IFNG +874 between pSS patients and controls. The erythrocyte sedimentation rate and concentrations of serum IgA and serum beta2 microglobulin were lower in pSS patients carrying the IL4 -590 T allele or the IL13 +2044 A allele than in those not carrying the respective alleles. The IL4 -509 T allele and IL13 +2044 A allele carriers less often had purpura than the corresponding non-carriers. CONCLUSIONS: The frequencies of the cytokine genotypes regulating Th1/Th2 differentiation did not differ between pSS patients and controls. However, the presence of cytokine genotypes with increased susceptibility to atopic and other Th2 diseases was associated with signs of a milder form of pSS. This finding would favour a hypothesis envisaging pSS as primarily a Th1 mediated autoimmune disease.

Aged↗
PubMed2004

Presence of apolipoprotein E epsilon4 allele predisposes to early onset of primary Sjogren's syndrome.

BACKGROUND: Apolipoprotein E (apoE) polymorphism plays a central role in lipid metabolism, but has recently also been suggested to regulate inflammation, as judged by levels of serum C-reactive protein (CRP). OBJECTIVE: To establish whether polymorphism of the apoE genes affects susceptibility to primary Sjogren's syndrome (pSS), degree of inflammation or age of onset of pSS. METHODS: ApoE genotype distribution and allelic frequencies were analysed using PCR and the TaqMan system in 63 Finnish Caucasian patients with pSS and in 64 healthy controls matched for sex, ethnic origin and area of residence. The clinical and immunological data on the pSS patients were analysed in relation to the apoE genotypes. RESULTS: There was no difference between pSS patients and controls in apoE genotype and allelic frequencies. The apoE epsilon4 allele was significantly associated with early onset of pSS in the entire population and in female patients (Kaplan-Meier log rank test, P = 0.0407 and P = 0.0168, respectively). The average age (+/- S.D.) of onset of pSS in all apoE epsilon4 allele carriers was 46 +/- 12 and in other genotypes it was 53 +/- 10 yr (P = 0.031, t-test). ApoE polymorphism was not associated with signs of inflammation evaluated by such markers as concentration of plasma CRP, plasma interleukin-6, plasma TNF-alpha, immunoglobulin G and haemoglobin, or leucocyte count or ESR. CONCLUSIONS: ApoE polymorphism does not affect susceptibility to pSS or levels of plasma inflammatory indices in patients with pSS. However, a clear association prevails between apoE epsilon4 and early onset of pSS.

Age of Onset↗
PubMed2004

Matrix metalloproteinase 9 (MMP-9) gene polymorphism and MMP-9 plasma levels in primary Sjogren's syndrome.

OBJECTIVES: To determine whether plasma matrix metalloproteinase 9 (MMP-9) and MMP9 (-1562C-->T) polymorphism have an effect on the disease phenotype in primary Sjogren's syndrome (pSS). METHODS: Plasma MMP-9 concentrations and polymorphism of the MMP9 gene were analysed in 66 patients with pSS. These data were studied in relation to the clinical data of the patients. The genetic data of patients were compared with the data of 66 healthy subjects. RESULTS: Plasma MMP-9 was higher in patients with definite pSS than in patients with possible pSS. This association was principally caused by higher plasma MMP-9 in patients with a positive Schirmer test and keratoconjunctivitis sicca. pSS patients with purpura, SS-A autoantibodies and RF had significantly lower plasma MMP-9 than patients without these characteristics. The overall MMP9 (-1562C-->T) allele frequencies were similar in patients and control subjects. The frequency of the allele T was higher in patients without Raynaud's phenomenon than in the control group. CONCLUSIONS: MMP9 (-1562C-->T) could not be used for risk assessment in pSS. The presence of the rarer allele T may decrease the risk of Raynaud's phenomenon in pSS. High plasma MMP-9 is indicative of definite pSS but may paradoxically have a preventive effect on the eruption of purpura and on the development of autoantibody reaction in pSS.

Aged↗
PubMed2002

The significance of mannan-binding lectin gene alleles in patients with primary Sjögren's syndrome.

OBJECTIVE AND METHODS: To investigate the significance or mannan-binding lectin (MBL) gene alleles in patients with primary Sjogren's syndrome (pSS). Genotypes were determined in 65 pSS patients and 138 controls. RESULTS: No difference in MBL genotype or allele frequencies was detected between the pSS patients and controls. However, when the effect of MBL genotypes on the diagnostic findings in pSS patients was assessed, none of the eight patients with 52/w genotype fulfilled four (definite) Californian criteria (P = 0.007). Among these eight the Chisholm-Mason histological grade was > or = 3 in only three (P = 0.017). Furthermore, the MBL concentration was lower in patients with 52/w genotype compared to those with wild-type (w/w) genotype (P = 0.035). CONCLUSION: Our findings suggest that MBL structural gene polymorphisms do not influence on susceptibility to pSS. However, MBL may be associated with salivary gland destruction in pSS, and its concentration may be comparable with the intensity of inflammatory reaction. Further studies are warranted to clarify the possible mechanisms involved.

Adult↗
PubMed2001

Genetic association between interleukin-10 promoter region polymorphisms and primary Sjögren's syndrome.

OBJECTIVE: To determine whether the haplotypes formed on the basis of single-base-exchange polymorphisms at positions -1082, -819, or -592 of the interleukin-10 (IL-10) gene predispose subjects to primary Sjögren's syndrome (SS). METHODS: The frequency of IL-10 polymorphisms was analyzed in 62 patients with primary SS and in 400 healthy subjects. These data were assessed for correlations with the concentration of IL-10 in the plasma. RESULTS: The frequency of the IL-10 GCC haplotype (G at position -1082, C at position -819, and C at position -592 of the IL-10 gene) was increased (P < 0.05, odds ratio [OR] 1.90, 95% confidence interval [95% CI] 0.955-3.62) and the frequency of the ACC haplotype decreased (P < 0.05, OR 0.443, 95% CI 0.257-0.764) in primary SS patients compared with healthy controls. Moreover, the frequency of the ATA haplotype was similar in primary SS patients and healthy controls, but the incidence of the GCC/ATA genotype was elevated in the primary SS patients (P < 0.05, OR 2.19, 95% CI 1.19-4.03). The concentration of plasma IL-10 was significantly higher in patients carrying the GCC haplotype than in non-carriers of GCC. CONCLUSION: These results suggest that the presence of the GCC haplotype or the GCC/ATA genotype and the absence of the ACC haplotype of the IL-10 gene are associated with an increased susceptibility to primary SS. This effect is probably mediated by the increased capability to produce IL-10 among carriers of the GCC haplotype.

Adolescent↗
PubMed2001

Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjögren's syndrome and correlate with the clinical manifestations of the disease.

OBJECTIVES: To determine whether plasma interleukin-6 (IL-6) and G/C base exchange polymorphism at position -174 of the IL6 gene have an effect on the clinical manifestations of primary Sjögren's syndrome (pSS). METHODS: Levels of circulating IL-6 protein and polymorphism of the IL6 gene were analysed in 66 patients with pSS and in 400 healthy subjects. These data were studied in relation to clinical data on the pSS patients. RESULTS: Plasma IL-6 was elevated in pSS patients compared with healthy controls. pSS patients with coeliac disease, pulmonary fibrosis or alveolitis or peripheral nervous system symptoms had significantly higher IL-6 levels than patients without these manifestations. IL-6 levels increased in parallel with the histological grade of minor salivary gland biopsy and the number of pSS criteria fulfilled. IL6 allele frequencies were similar in patients and normal subjects. Plasma IL-6 levels were regulated by the IL6 genotype in pSS patients. CONCLUSIONS: The G/C polymorphism of the IL6 gene does not predispose patients to pSS, but the circulating IL-6 concentration is related to specific manifestations of the disease and the levels of IL-6 are regulated by the IL6 promoter polymorphism in pSS.

Adolescent↗
PubMed1999

Increased in vitro production of interleukin 6 in response to trimethoprim among persons with trimethoprim induced systemic adverse reactions.

OBJECTIVE: Trimethoprim occasionally triggers a systemic adverse reaction including fever, malaise, head and backache, and even overt meningeal irritation, particularly in women with an autoimmune rheumatic disease. To study the unknown pathogenesis of the reaction we measured the effect of trimethoprim upon the cytokine [interleukin (IL) 2, 6, 10, and tumor necrosis factor-alpha] production of trimethoprim reactive and tolerant persons' peripheral blood mononuclear cells in vitro. METHODS: Peripheral blood mononuclear cells from 12 women reactive to trimethoprim (3 with primary Sjögren's syndrome, 3 with systemic lupus erythematosus, 1 with systemic scleroderma, 5 with no rheumatic disease) were cultured in the presence of trimethoprim, and the cytokine production was measured. Eleven women who tolerated trimethoprim (6 with Sjögren's syndrome and 5 with no rheumatic disease) served as controls. RESULTS: Therapeutic trimethoprim concentration induced in the mononuclear cells of the trimethoprim reactive patients significantly higher IL-6 production [mean +/- SD (median), 2034+/-2965 (572) pg/ml] versus cells of the trimethoprim tolerant subjects [954+/-2552 (89) pg/ml; p = 0.036]. No significant differences in the production of other cytokines were detected. CONCLUSION: Trimethoprim induces IL-6 production in the peripheral blood mononuclear cells of trimethoprim reactive persons. We suggest that IL-6 production is the probable trigger leading to the clinical reaction.

Adult↗
PubMed1997

Severe antibody-mediated human insulin resistance: successful treatment with the insulin analog lispro. A case report.

OBJECTIVE: To evaluate the efficacy of the insulin analog lispro (Lys B28, Pro B29) in severe insulin resistance caused by human insulin antibodies. CASE: A 27-year-old man with a history of diabetes treated with human insulin for 3 years developed severe immunological insulin resistance caused by human insulin antibodies. Throughout follow-up (12 months) the insulin analog lispro was administered with an infusion pump as the only insulin therapy. The insulin dose decreased from an average of 300 U/day to 58 U/day, HbA1c decreased from 12.6 to 7.4%, and human insulin antibodies decreased from 8,057 to 1,860 nU/ml. Hypoglycemic episodes during early morning disappeared. CONCLUSIONS: The insulin analog lispro might be suitable for the treatment of diabetic patients with substantially increased insulin antibody levels Apparently, the structural difference between the lispro and human insulin molecules prevented lispro from binding to the human insulin antibodies in this patient and consequently was nonimmunogenic.

Adult↗
PubMed1996

Intravenous calcitriol therapy restores reduced antigen-induced T-lymphocyte response in 1,25-(OH)2D3-deficient hemodialysis patients.

Ten hemodialysis patients were treated with intravenous calcitriol (1-1.5 micrograms 3 times per week) for 3 months and parameters reflecting cell-mediated immunity were measured before and at the end of treatment. Peripheral blood CD4+ cells increased from 33.1 +/- 14.2 to 43.8 +/- 5.8% (p < 0.05) causing a comparable increase in CD3+ cells (67.3 +/- 14.3 vs. 77.1 +/- 7.9%, p < 0.05), whereas CD8+ cells did not change significantly (22.2 +/- 5.4 vs. 25.5 +/- 3.0%). Mitogen-induced lymphocyte stimulation responses were normal even before treatment and did not change. Antigen-induced T-cell responses were very heterogeneous before calcitriol therapy; those 5 with initially unmeasurably low serum 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) had a weaker response than the other patients (3,873 +/- 1,528 vs. 22,948 +/- 13,684 cpm, p < 0.05). After calcitriol treatment the patients with pretherapy unmeasurably low serum 1,25-(OH)2D3 had a comparable response to other patients (16,220 +/- 9,674 vs. 22,064 +/- 10,331 cpm). Our study shows that calcitriol therapy restores the depressed antigen-induced T-cell response of the hemodialysis patients most deficient in 1,25-(OH)2D3.

Adult↗
PubMed1988

Oral candidal infection as a sign of HIV infection in homosexual men.

The oral mucosae of 66 homosexual men were examined clinically and by means of cultivation to determine the presence of Candida infection. In addition, clinically detected mucosal changes were recorded and a biopsy specimen was obtained for the histopathologic classification. A total of forty one subjects (62%) showed clinical evidence of candidiasis. Fourteen (21%) of the sixty-six men were seropositive for human immunodeficiency virus (HIV). A total of thirteen of fourteen (93%) of the seropositive men and twenty-six of fifty-two (50%) of the HIV seronegative men had culture-confirmed oral candidiasis. In the latter group, oral candidiasis was clearly correlated to cigarette smoking. Clinical mucosal changes other than candidiasis were found in forty-five of the sixty-six subjects studied. The most frequent finding was trauma resulting from biting, which was usually localized on the cheek. Leukoplakia was found in twelve of sixty-six subjects, while cauliflower-like condylomas were present in 4 persons. The results emphasize the frequent occurrence of different oral lesions in subjects seropositive for HIV and in those at high risk for HIV infection. Oral examination in search for potential early manifestations of HIV infection in homosexual men is advocated.

Alcohol Drinking↗
PubMed1988

Human milk fat globule antigen III D 5, steroid receptors and histopathologic parameters in breast cancer.

Immunohistochemical reactivity of mammary carcinomas with the monoclonal human milk fat globule (HMFG) antibody III D 5, and the estrogen receptor (ER) and progesterone receptor (PR) status were compared with the histopathology of primary breast cancer. The reactivity with III D 5 has earlier been shown to be associated with the estrogen receptor status of tumours and with a favourable prognosis. The reactivity of tumours with III D 5, as well as the presence of ER and PR correlated significantly with the histological features of differentiation; histological grade, nuclear grade, tumour necrosis and lymphoid infiltration. Reactivity with III D 5 correlated with all these parameters, while the presence of ER did not correlate with the nuclear grade and that of PR correlated only with the nuclear grade and the lymphoid infiltration of tumours. Reactivity of III D 5 may thus have prognostic and therapeutic implications in the management of breast cancer.

Adult↗
PubMed1988

Defective autologous mixed leukocyte reaction in newly diagnosed type 1 diabetes mellitus.

We studied autologous mixed leukocyte reaction (AMLR) in type 1 (insulin-dependent) diabetes mellitus (IDDM) patients, their healthy siblings and healthy schoolchildren, Blood samples from the patients were drawn within 1 week after hospitalization and 2 months later. AMLR was significantly depressed in the patients when compared to healthy siblings or other healthy controls. In addition, the mean AMLR responsiveness of the healthy control group exceeded that of healthy siblings. The production of IL-2 in AMLR was impaired in the patient group and the defective AMLR could be restored by addition of exogenous IL-2 in 7-10 patient cultures. However, in 3-10 patients addition of IL-2 induced no enhancement of proliferation. While the patients in general had raised levels of activated T lymphocytes these three patients had higher numbers of activated T cells than other patients. Defective AMLR and presence of activated T cells may be related and may play a role in the pathogenesis of IDDM.

Adolescent↗
PubMed1987

Long latency precedes overt seroconversion in sexually transmitted human-immunodeficiency-virus infection.

Signs of latent HIV infection were sought in stored serum samples collected before overt seroconversion, confirmed by enzyme-linked immunosorbent assay (ELISA), from 9 subjects with human-immunodeficiency-virus (HIV) infection, in serum from 25 seronegative sexual partners of HIV-seropositive men and from 23 other seronegative, homosexually active men. Free HIV antigen and/or low-titre antibodies to recombinant structural (core, env) or non-structural (3' orf, sor, tat) proteins were seen 6-14 months before seroconversion in all 9 subjects who seroconverted. Antibodies against core proteins detected by western blot were usually the first sign of latent HIV infection. 5 of the 25 ELISA-negative exposed partners have shown HIV antigenaemia and antibodies against core proteins for 16-34 months. By in-situ hybridisation, HIV-specific RNA was detected in peripheral-blood non-lymphoid mononuclear cells in some of the latently infected partners. All subjects with latent HIV infection had normal numbers of T4 lymphocytes but half of them lost their in-vitro proliferative T-cell response to a recall antigen (purified protein derivative of tuberculin). Early HIV infection, characterised by a low-level and restricted antibody response towards HIV core and regulatory proteins, seems mainly to affect antigen-presenting cells.

Acquired Immunodeficiency Syndrome↗
PubMed1987

The use of an HTLV-I-infected human T-cell line (ATH8) in an interleukin-2 bioassay.

Biological interleukin-2 (IL-2) assays require cells that proliferate only in the presence of IL-2. The most often used human cells for this purpose have been phytohaemagglutinin (PHA)-stimulated buffy coat lymphocytes made dependent on IL-2. The results obtained by this T-blast method have not been easily reproducible and/or comparable due to differences in individual buffy coat batches. Murine cytotoxic T-cell lines (CTLL and CTLL-2) have been widely used in human IL-2 assays, but there remains a need for a human cell line. We have developed an IL-2 bioassay, based on the use of a human HTLV-I-infected Th-cell line, ATH8. These cells express IL-2 receptor and are totally dependent on extrinsic IL-2 for proliferation. The results of the ATH8 IL-2 assay were reproducible and comparable to those obtained with successful T-blast assays. ATH8 cells do not require a prolonged culture period before they are suitable for the IL-2 assay as do T-blasts.

Biological Assay↗
PubMed1987

Acute multiple sclerosis exacerbations are characterized by low cerebrospinal fluid suppressor/cytotoxic T-cells.

The present study describes peripheral blood (PB) and CSF T-lymphocyte subpopulations in 55 MS patients with and without acute exacerbation and compares the results with those obtained from 8 with CNS infections and 45 with other neurological disorders or symptoms (OND). The MS patients were most strongly characterized by a decline of their CSF suppressor/cytotoxic T-cells, which was most profound during acute exacerbations. The proportional amount of CSF helper/inducer T-cells (Th) was higher in both MS group than in the OND group, but not different from that of the CNS infection group. No statistically significant change in the CSF Th-cells during exacerbations was seen. MS patients without an exacerbation had somewhat higher levels of their PB Th-cells than the patients with OND, but otherwise no differences in the PB T-cell subsets were seen.

Cerebrospinal Fluid↗