Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 105
Filter
Add more filters

Country/Region as subject
Publication year range
1.
Rheumatology (Oxford) ; 59(9): 2350-2359, 2020 09 01.
Article in English | MEDLINE | ID: mdl-31873754

ABSTRACT

OBJECTIVE: To characterize the systemic phenotype of primary Sjögren's syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. METHODS: The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren's syndrome from the five continents. RESULTS: The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P < 0.001) compared with females, as did patients diagnosed at <35 years (6.7 vs 5.6 in patients diagnosed at >65 years, P < 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P < 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P < 0.001). CONCLUSION: The systemic phenotype of primary Sjögren's syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.


Subject(s)
Ethnicity/statistics & numerical data , Racial Groups/statistics & numerical data , Sjogren's Syndrome/epidemiology , Black or African American/statistics & numerical data , Asian People/statistics & numerical data , Cohort Studies , Female , Hispanic or Latino/statistics & numerical data , Humans , Information Dissemination , Male , Middle Aged , Phenotype , Registries , Severity of Illness Index , Sjogren's Syndrome/ethnology , White People/statistics & numerical data
2.
Clin Exp Rheumatol ; 36 Suppl 112(3): 102-112, 2018.
Article in English | MEDLINE | ID: mdl-30156539

ABSTRACT

OBJECTIVES: To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjögren's syndrome (SjS). METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays. RESULTS: By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti- La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglo-bulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for cryoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESS- DAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains). CONCLUSIONS: We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.


Subject(s)
Autoantibodies/blood , Complement C3/analysis , Complement C4/analysis , Cryoglobulins/analysis , Sjogren's Syndrome/immunology , Adult , Aged , Antibodies, Antinuclear/blood , Biomarkers/blood , Female , Humans , Male , Middle Aged , Phenotype , Prognosis , Registries , Rheumatoid Factor/blood , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/epidemiology
3.
Ann Rheum Dis ; 76(6): 1042-1050, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27899373

ABSTRACT

OBJECTIVES: To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed. RESULTS: We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69). CONCLUSIONS: This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.


Subject(s)
Asian People/statistics & numerical data , Black or African American/statistics & numerical data , Hispanic or Latino/statistics & numerical data , Registries , Sjogren's Syndrome/ethnology , White People/statistics & numerical data , Adult , Aged , Antibodies, Antinuclear/blood , Cross-Sectional Studies , Eye Diseases/etiology , Female , Humans , Male , Middle Aged , Phenotype , Prevalence , Sjogren's Syndrome/blood , Sjogren's Syndrome/complications , Sjogren's Syndrome/diagnosis , Spatial Analysis
4.
Mediators Inflamm ; 2016: 4328372, 2016.
Article in English | MEDLINE | ID: mdl-26884645

ABSTRACT

Recently, we reported elevated proportions of circulating follicular T helper cells and higher levels of interleukin- (IL-) 21 in primary Sjögren's syndrome (pSS). Interaction of invariant natural killer T (iNKT) cells with B cells and granzyme B (GrB) production may be also important in pSS. Thirty-two pSS patients and 24 healthy controls were enrolled in our study. We investigated the expression of intracellular GrB and IL-21 receptor (IL-21R) of CD19(+)CD5(+) and CD19(+)CD5(-) B cells; furthermore, we determined the IL-21 expression of iNKT cells as well. We also assessed the proportion of transitional (CD19(+)CD24(high)CD38(high)), mature (CD19(+)CD24(int)CD38(int)) and primarily memory (CD19(+)CD24(high)CD38(-)) B cells. CD5(+) but not CD5(-) B cells showed elevated GrB and IL-21R expression in pSS; additionally IL-21 expression of iNKT cells was also elevated. The ratios of transitional and mature B cells were elevated in pSS, while primarily memory B cell percentages were decreased, which correlated with GrB and IL-21R expression of CD19(+) B cells. Our results suggest that enhanced IL-21R expression of CD19(+)CD5(+) B cells and production of IL-21 by iNKT cells may play an important role in the pathogenesis of pSS by regulating CD19(+)CD5(+) B cell functions and increasing GrB production, presumably leading to a counter-regulatory effect in the disease.


Subject(s)
B-Lymphocytes/metabolism , CD5 Antigens/metabolism , Granzymes/metabolism , Interleukins/metabolism , Sjogren's Syndrome/metabolism , ADP-ribosyl Cyclase 1/metabolism , Adult , Antigens, CD19/metabolism , Female , Humans , Male , Middle Aged , Receptors, Interleukin-21/metabolism
5.
Acta Derm Venereol ; 95(2): 151-5, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24890798

ABSTRACT

Our aim was to assess whether the presence of highly active effector T cells in atopic dermatitis (AD) is associated with changes in the number and/or function of regulatory T cells (Tregs). Flow cytometry was utilised to determine the percentage of CD4+ CD25bright CD127-/low FOXP3+ and skin-homing CLA+ CD4+ CD25bright FOXP3+ Tregs in healthy controls and AD patients. The correlation between disease severity and Treg percentages was estimated. Treg suppressor activity and cell proliferation were measured after T-cell stimulation. Significantly increased percentages of Tregs were found in AD patients compared to healthy individuals, and significant correlation between the frequency of Tregs and disease severity was also detected. The otherwise normal suppressor activity of Tregs decreased in the presence of Staphylococcus enterotoxin B (SEB). In conclusion, the continuous presence of SEB can trigger an acquired functional impairment of Tregs in AD patients and the correlation between the increased frequency of Tregs and disease severity supports their important role in AD pathogenesis.


Subject(s)
Dermatitis, Atopic/immunology , Skin/immunology , T-Lymphocytes, Regulatory/immunology , Adolescent , Adult , Antigens, Differentiation, T-Lymphocyte/metabolism , Biomarkers/metabolism , Case-Control Studies , Cell Separation/methods , Cells, Cultured , Child , Child, Preschool , Coculture Techniques , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/metabolism , Enterotoxins/pharmacology , Female , Flow Cytometry , Forkhead Transcription Factors/metabolism , Humans , Immunophenotyping/methods , Interleukin-2 Receptor alpha Subunit/metabolism , Interleukin-7 Receptor alpha Subunit/metabolism , Lymphocyte Activation , Male , Membrane Glycoproteins/metabolism , Predictive Value of Tests , Severity of Illness Index , Skin/metabolism , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/metabolism , Young Adult
6.
Rheumatol Int ; 34(5): 717-20, 2014 May.
Article in English | MEDLINE | ID: mdl-23612780

ABSTRACT

The objective of the study was to investigate the possibility whether the in vitro treatment with vitamin D3 can restore the impaired expression of protein kinase C (PKC) isoenzymes and IL-2 production in the lymphocytes of patients with systemic lupus erythematosus (SLE). Purified T lymphocytes from 14 patients with SLE and 13 healthy controls were cultured for 48 h in the presence and absence of 1 and 100 nM doses of vitamin D3. The expressions of various PKC isoenzymes were tested by Western blot analysis, and the amounts of various cytokines were detected by ELISA in the culture supernatants. Neither the low (1 nM) nor the high (100 nM) doses of vitamin D3 (1α,-25-dihydroxyvitamin) applied in vitro for 48 h were able to restore the decreased expression of PKC isoenzymes in the T cells of SLE patients. However, 100 nM of vitamin D3 significantly increased the release of IL-10, but suppressed the production of IL-2, IL-6, interferon γ and TNF α in the culture supernatants of both groups. As the low production of IL-2 is one of the main pathologic features of SLE, we recommend to avoid the use of high doses of vitamin D3 for treatment of lupus patients with vitamin D3 deficiency.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Calcitriol/pharmacology , Interleukin-2/metabolism , Lupus Erythematosus, Systemic/enzymology , Lupus Erythematosus, Systemic/immunology , Protein Kinase C/metabolism , T-Lymphocytes/drug effects , Adult , Aged , Case-Control Studies , Cells, Cultured , Dose-Response Relationship, Drug , Down-Regulation , Female , Humans , Isoenzymes , Male , Middle Aged , Signal Transduction , T-Lymphocytes/enzymology , T-Lymphocytes/immunology
7.
Mediators Inflamm ; 2014: 631787, 2014.
Article in English | MEDLINE | ID: mdl-25177110

ABSTRACT

Recently, we revealed the importance of follicular helper T cells (T(FH)) in the pathogenesis of primary Sjögren's syndrome (pSS). In the present study, we focused on the site of the inflammation and determined the composition of lymphocyte infiltration in labial salivary gland (LSG) biopsies with special emphasis on T(FH) and germinal center B cells. We selected tissue blocks obtained from ten patients at the time of disease onset. Detection of cell specific markers was performed with immunohistochemical and immunofluorescence stainings. We evaluated patients' clinical and laboratory features retrospectively and assessed the relation between disease course and early histopathological findings. LSG biopsies were graded based on the extension and arrangement level of periductal inflammatory cell infiltrates. T(FH) cell markers (CD84, PD-1, and Bcl-6) occurred predominantly in more organized structures with higher focus scores. The coexpression of CD3 and Bcl-6 markers clearly identified T(FH) cells close to Bcl-6(+) B cells with the typical formation of germinal centers. Systemic features were developed later in the disease course only in patients with highly structured infiltrates and the presence of T(FH) cells. Our observations suggest that the presence of T(FH) cells in LSGs at the disease onset may predict a more pronounced clinical course of pSS.


Subject(s)
Inflammation/immunology , Inflammation/pathology , Salivary Glands/immunology , Salivary Glands/pathology , Sjogren's Syndrome/immunology , Sjogren's Syndrome/pathology , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/pathology , Aged , Female , Humans , Immunohistochemistry , In Vitro Techniques , Male , Middle Aged
8.
Clin Immunol ; 147(2): 95-104, 2013 May.
Article in English | MEDLINE | ID: mdl-23578551

ABSTRACT

The aim of this study was to investigate the possible role of follicular helper T (TFH) cells in the pathogenesis of primary Sjögren's syndrome (pSS) by analyzing immune-competent cells and serological markers with special emphasis on clinical symptoms. We enrolled 50 pSS patients and 16 healthy individuals in the study. Patients had elevated ratio of peripheral TFH cells, however, when dividing patients into two groups defined by the presence of extraglandular manifestations (EGMs), only patients with EGMs differed from controls significantly. Moreover, TFH cell percentages correlated positively with both activated T cell and Tr1 cell values. On the contrary, TFH cell percentages showed negative correlation with both IgM and IgG memory B cell proportions. Elevated TFH percent\ages were observed in the anti-SSA/SSB positive patients, and also in patients with higher IL-12, IL-21 levels and focus score values. Increased TFH cell proportions seem to have an important role in disease development.


Subject(s)
Sjogren's Syndrome/immunology , T-Lymphocytes, Helper-Inducer/immunology , Aged , Autoantibodies/immunology , Autoantigens/immunology , Case-Control Studies , Cytokines/blood , Female , Humans , Male , Middle Aged , Ribonucleoproteins/immunology , SS-B Antigen
9.
Orv Hetil ; 154(40): 1571-8, 2013 Oct 06.
Article in Hungarian | MEDLINE | ID: mdl-24077160

ABSTRACT

Vasculitis is a heterogeneous group of rare disorders in which inflammation of blood vessels is the common feature. Due to the increasing number of diseases as well as overlaps and gaps in the definition and nomenclature, the classification criteria were constantly changing in the past decades. The classifications were based essentially on the size of affected blood vessels and pathologic characteristics of inflamed vessel walls. The standard procedures and validated diagnostic criteria are missing from the diagnostics of vasculitis, thus in clinical practice the classification criteria are applicable. The 2012 Chapel Hill Consensus Conference brought a change in the definition, nomenclature and classification of previously uncategorized diseases. The definitions of subgroups accurately determine the diagnosis of the specific disease, and they are suitable for establishing homogeneous disease groups. By better understanding of the etiopathogenetic factors, further diseases and subgroups may be defined in the near future.


Subject(s)
Vasculitis/classification , Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Behcet Syndrome/diagnosis , Churg-Strauss Syndrome/diagnosis , Cogan Syndrome/diagnosis , Consensus , Consensus Development Conferences as Topic , Cryoglobulinemia/complications , Granulomatosis with Polyangiitis/diagnosis , Humans , IgA Vasculitis/diagnosis , Microscopic Polyangiitis/diagnosis , Mucocutaneous Lymph Node Syndrome/diagnosis , Polyarteritis Nodosa/diagnosis , Terminology as Topic , Vasculitis/etiology
10.
Clin Immunol ; 142(2): 150-9, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22036269

ABSTRACT

The aim of this study was to evaluate the clinical and immunomodulatory effects of extracorporeal photochemotherapy (ECP) in systemic sclerosis (SSc). We enrolled 16 patients with diffuse cutaneous SSc, who received 12 ECP treatments in total. After ECP treatments, the dermal thickness reduced and the mobility of joints improved. Internal organ involvement did not deteriorate. The percentages and numbers of peripheral Th17 cells decreased, the values of Tr1 and Treg cells increased, and the suppressor capacity of Treg cells improved. Interestingly, we found a positive correlation between the reduction of IL-17 levels and skin thickness measured by ultrasound. Moreover, levels of CCL2 and TGF-beta decreased, while the concentration of IL-1Ra, IL-10 and HGF elevated during the therapy. ECP treatments contribute to the restoration of disproportional autoimmune responses and attenuate fibrotic processes, thus decelerate the disease progression. Accordingly, ECP can be a useful element of novel treatment modalities proposed for SSc.


Subject(s)
Cytokines , Methoxsalen/therapeutic use , Photopheresis/methods , Scleroderma, Systemic , Adult , Case-Control Studies , Combined Modality Therapy , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Male , Middle Aged , Scleroderma, Systemic/immunology , Scleroderma, Systemic/radiotherapy , Skin/diagnostic imaging , Skin/pathology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/radiation effects , Th17 Cells/drug effects , Th17 Cells/radiation effects , Ultrasonography
11.
Orv Hetil ; 153(12): 454-60, 2012 Mar 25.
Article in Hungarian | MEDLINE | ID: mdl-22411218

ABSTRACT

UNLABELLED: Systemic lupus erythematosus is a chronic autoimmune disorder which affects women with child bearing potential. AIM: The aim of this study was to investigate the successful pregnancies in patients with lupus in the past 10 years. Women were followed up at the 3rd Department of Internal Medicine, University of Debrecen. RESULTS: During this investigated period, 26 patients became pregnant. Seven patients had a positive history for lupus before the pregnancy. A total of 29 children were born. The mean gestational age was 35 weeks. The average birth weight was 2415 grams. Toxemic pregnancy was the most common complication found in 9 patients. Lupus nephritis activity occurred in 2 patients, and 1 of them had it for the first time during the course of her disease. CONCLUSIONS: In the past years, the number of pregnancies in patients with lupus has been increasing. Due to proper patient care and education, the outcome is more favourable.


Subject(s)
Immunosuppressive Agents/administration & dosage , Live Birth , Lupus Erythematosus, Systemic/drug therapy , Pregnancy Complications/immunology , Adrenal Cortex Hormones/administration & dosage , Adult , Aspirin/administration & dosage , Azathioprine/administration & dosage , Birth Weight , Female , Follow-Up Studies , Gestational Age , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Immunoglobulins, Intravenous/administration & dosage , Pregnancy , Pregnancy Complications/therapy
12.
Orv Hetil ; 153(32): 1281-3, 2012 Aug 12.
Article in Hungarian | MEDLINE | ID: mdl-22878037

ABSTRACT

Ramsay Hunt syndrome is a special form of herpes zoster which is typically characterized by peripheral facial palsy and unilateral herpetic vesicles on the ear. These symptoms are often accompanied by vestibulocochlear dysfunction and other neurological and ophthalmological symptoms. The diagnosis and therapy requires a multidisciplinary approach. The authors present a typical case where the early administration of combined antiviral and systemic corticosteroid therapy led to complete recovery. The authors emphasize the importance of early diagnosis and adequate combination therapy, which improves the prognosis of this disease.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Antiviral Agents/therapeutic use , Facial Paralysis/virology , Herpes Zoster Oticus/diagnosis , Herpes Zoster Oticus/drug therapy , Immunocompromised Host , Acyclovir/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Adult , Antiviral Agents/administration & dosage , Drug Therapy, Combination , Early Diagnosis , Female , Herpes Zoster Oticus/complications , Humans , Interdisciplinary Communication , Treatment Outcome
13.
Orv Hetil ; 153(13): 483-98, 2012 Apr 01.
Article in Hungarian | MEDLINE | ID: mdl-22430004

ABSTRACT

Atherosclerosis is a systemic disease affecting the coronary, carotid, intracerebral, renal and peripherial arteries. The early morphological and functional impairments could be detected in the second or third decades of life and their progression depend on the number and severity of risk factors and individual susceptility. Although the vascular risk factors (smoking, overweight, age, unhealthy diet, lack of physical exercise, hypertension, diabetes mellitus, chronic kidney disease and dyslipidemia) are the same and common in the different vascular diseases, the present clinical routine artificially classifies the diagnosis and therapy of different vascular diseases into different subfields of medicine with the negative impact of possible polypragmasia. Recently, worldwide health surveys (e.g. REACH registry) have proven the usefulness of a holistic approach in the diagnosis and therapy of multiorgan-affected vascular patients. This review summarizes the multidisciplinary advances and future perspective of vascular diseases.


Subject(s)
Autoimmune Diseases/complications , Diabetes Mellitus, Type 2/complications , Dyslipidemias/complications , Kidney Diseases/complications , Vascular Diseases/diagnosis , Vascular Diseases/therapy , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/therapy , Atrial Fibrillation/diagnosis , Atrial Fibrillation/therapy , Autoimmune Diseases/diagnosis , Autoimmune Diseases/therapy , Carotid Stenosis/diagnosis , Carotid Stenosis/therapy , Chronic Disease , Diabetes Complications/diagnosis , Diabetes Complications/therapy , Dyslipidemias/diagnosis , Dyslipidemias/therapy , Humans , Hypertension/diagnosis , Hypertension/therapy , Interdisciplinary Communication , Kidney Diseases/diagnosis , Kidney Diseases/physiopathology , Kidney Diseases/therapy , Risk Factors , Vascular Diseases/complications , Vascular Diseases/etiology , Vascular Diseases/immunology , Vascular Diseases/pathology , Vascular Diseases/prevention & control
14.
Magy Onkol ; 56(1): 50-4, 2012 Mar.
Article in Hungarian | MEDLINE | ID: mdl-22403762

ABSTRACT

Scleroderma is the general disease of the connective tissue, which can be characterized by the proliferation of the connective tissue and fibrosis. According to the results of international studies scleroderma is frequently accompanied by neoplastic diseases, among which the most often occurring is the neoplastic pathology of the breast and the lungs. In May 2007, in the case of our 40-year-old woman patient the histological examination of the tumor we noticed in the left breast verified invasive carcinoma. In December 2007, after neoadjuvant chemotherapy she had a left mastectomy and then she was given postoperative irradiation, hormone therapy and trastuzumab (Herceptin) treatment, which was suspended in December 2008 due to oedema and fibrosis all over the body. In May 2009 she first visited the immunology outpatient department of our clinic, where we started her examination because of our suspicion of scleroderma and her cutaneous fibrosis symptoms, which was established on the basis of the examinations (immunoserology, body plethysmography, diffusing capacity of the lung for carbon monoxide, capillary microscopy, barium swallow) and her symptoms. She was given a conservative therapy (pentoxyphylline, amlodipine, nitroglycerin). Scleroderma arising after the neoplastic process of the breast is usually much more progressive than the primary disease. International reports also show a close correlation between breast cancer and the development of scleroderma, but its exact mechanism is not yet clear.


Subject(s)
Breast Neoplasms/complications , Carcinoma, Ductal, Breast/complications , Lung/pathology , Scleroderma, Systemic/complications , Scleroderma, Systemic/diagnosis , Skin/pathology , Adult , Amlodipine/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/therapy , Chemotherapy, Adjuvant , Edema/etiology , Female , Fibrosis/etiology , Humans , Lung/diagnostic imaging , Neoadjuvant Therapy/methods , Nitroglycerin/administration & dosage , Pentoxifylline/administration & dosage , Radiography , Radiotherapy, Adjuvant , Scleroderma, Systemic/drug therapy , Vasodilator Agents/administration & dosage
15.
J Clin Immunol ; 31(5): 864-72, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21691938

ABSTRACT

BACKGROUND: Conflicting data exist on the number of invariant NKT (iNKT) cells in atopic dermatitis (AD); furthermore, no data have been published on their functional capacity. METHODS: The frequency and number of circulating CD3+6B11+ iNKT cells and their CD4+ and CD4- subpopulations were evaluated in peripheral blood obtained from 41 patients with AD by four-color flow cytometry. Likewise, functional properties of iNKT cells were measured by five-color intracellular cytokine staining. RESULTS: The number and percentage of total iNKT cells and their CD4/CD8 subpopulations were significantly lower than the controls. Of further importance, the CD4-CD8- (double negative, DN) iNKT subgroup showed the strongest positive correlation with total iNKT cells. In addition, the DN subgroup exhibited the most pronounced functional alteration with significantly decreased levels of intracellular IFNγ and significantly increased levels of intracellular IL-4 in AD patients compared with the controls. CONCLUSION: The significantly altered number and cytokine production of iNKT cells from AD patients suggests that these cells may play an important role in the pathogenesis of AD.


Subject(s)
Dermatitis, Atopic/immunology , Dermatitis, Atopic/pathology , Interferon-gamma/metabolism , Interleukin-4/metabolism , Natural Killer T-Cells/metabolism , Adolescent , Adult , CD4 Antigens/metabolism , Cell Count , Cell Separation , Cells, Cultured , Child , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/physiopathology , Female , Flow Cytometry , Gene Expression Regulation/immunology , Humans , Immunophenotyping , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-4/genetics , Interleukin-4/immunology , Male , Natural Killer T-Cells/immunology , Natural Killer T-Cells/pathology , Th1-Th2 Balance
16.
Microvasc Res ; 82(1): 84-7, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21515290

ABSTRACT

OBJECTIVES: Calcium channel inhibitors have beneficial impact on microcirculation, but beta-blocker effect is controversial. Clinicians still do not agree on beta-blocker combination with other treatments in the management of impaired microcirculation. The aim of the present study was to describe the effects of beta-blocker metoprolol monotherapy and combined with calcium channel inhibitor felodipin on digital microcirculation in primary Raynaud's syndrome. METHODS: We enrolled in this study 46 patients suffering from both hypertension and primary Raynaud's syndrome. Fifteen patients were treated with beta-blocker monotherapy (metoprolol), 13 received combined beta-blocker and calcium channel blocker therapy (felodipin and metoprolol), while 18 patients without any medications served as controls. Measurement of digital microcirculation was carried out with laser Doppler scanner. RESULTS AND CONCLUSIONS: Our investigation concludes that the concurrent administration of beta-blockers with calcium channel inhibitors positively reduces symptoms in patients suffering from Raynaud's syndrome.


Subject(s)
Felodipine/therapeutic use , Fingers/blood supply , Metoprolol/therapeutic use , Microcirculation/drug effects , Raynaud Disease/drug therapy , Adult , Drug Therapy, Combination/methods , Felodipine/pharmacology , Female , Humans , Hyperemia/physiopathology , Hypertension/complications , Hypertension/physiopathology , Laser-Doppler Flowmetry , Metoprolol/pharmacology , Microcirculation/physiology , Middle Aged , Raynaud Disease/complications , Raynaud Disease/physiopathology , Treatment Outcome
17.
Int Immunol ; 22(7): 605-9, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20497955

ABSTRACT

OBJECTIVES: The aim of the study was to examine human serum paraoxonase 1 (PON1) activity, phenotype distribution and lipid parameters in patients with Sjögren's syndrome. The prevalence of cardio- and cerebrovascular diseases in SS patients was also evaluated after a 5-year follow-up. METHODS: Fifty-seven SS patients and 17 age-matched healthy controls were enrolled into the study. PON1 and arylesterase activities were measured spectrophotometrically. The phenotype distribution of PON1 was determined by the dual-substrate method. RESULTS: Significantly lower PON1 activity was found in patients with SS compared with the control group (98.00 +/- 69.21 versus 203.3 +/- 92.78 U ml(-1); P < 0.001). There were significant differences in PON1 phenotype distribution of SS patients and controls (AA/AB/BB: 91.2/8.8/0 versus 58.8/29.4/11.8%; P < 0.01). No significant correlations were found between PON activity and disease-characteristic autoantibodies, including anti-Ro/SS-A and anti-La/SS-B concentrations. PON activity did not predict the cerebro/cardiovascular risk in SS patients during the 5-year follow-up. CONCLUSIONS: Despite the relatively small sample size that reduces the power of the study, decreased PON activity may be a possible cardiovascular risk factor in SS. Disadvantageous PON1 phenotype distribution may contribute to the decreased PON activity in these patients.


Subject(s)
Aryldialkylphosphatase/metabolism , Sjogren's Syndrome/enzymology , Autoantibodies/immunology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Phenotype , Sjogren's Syndrome/immunology
18.
Rheumatology (Oxford) ; 49(2): 211-7, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19946023

ABSTRACT

OBJECTIVE: The aim of the present study was to investigate the immunomodulating role of fat-soluble vitamins in 25 patients with primary SS (pSS) and 15 healthy individuals. METHODS: Plasma levels of vitamins A, D and E were determined by HPLC. Peripheral NK, NK T cells, T-cell subsets, B cells, IL-10 producing Tr1 cells, CD4(+)CD25(+) Treg cells and Th17 were determined by flow cytometry. Various Th1- and Th2-soluble cytokines were assessed by ELISA, whereas intracytoplasmic cytokines (IFN-gamma, IL-4, -10 and -17) were measured by flow cytometry. Correlation was assessed between vitamin levels and immunological and clinical parameters. RESULTS: Vitamin A levels did not differ between patients and controls, yet in patients with extraglandular manifestations (EGMs) a significant decrease in vitamin A levels was apparent compared with pSS patients without EGMs (P = 0.005). Vitamin E levels were increased in patients compared with controls (P = 0.004), whereas vitamin D levels were similar in pSS and control subjects. In patients, vitamin A showed a positive correlation with both NK cell (P = 0.038) and Th17 cell (P = 0.025), and a negative correlation with Schirmer's test values (P = 0.035). Positive correlation was found between vitamin E and NK cells (P = 0.043), Th1 cells (P = 0.049) and the Th1/Th2 ratio (P = 0.043). In the control group, we found correlation between vitamin E and serum IL-10 levels (P = 0.003). CONCLUSIONS: Our data suggest that fat-soluble vitamins may be important in immunoregulatory processes in patients with pSS.


Subject(s)
Sjogren's Syndrome/immunology , Vitamins/immunology , Aged , Cytokines/blood , Female , Humans , Interleukin-10/blood , Killer Cells, Natural/immunology , Lymphocyte Subsets/immunology , Male , Middle Aged , Th1 Cells/immunology , Th2 Cells/immunology , Vitamin A/immunology , Vitamin D/immunology , Vitamin E/immunology
19.
Clin Endocrinol (Oxf) ; 72(5): 641-7, 2010 May.
Article in English | MEDLINE | ID: mdl-19863576

ABSTRACT

OBJECTIVE: Autoimmune polyendocrine syndrome type I (APS I) is a rare primary immunodeficiency disorder characterized by chronic mucocutaneous candidiasis, multi-organ autoimmunity and ectodermal dysplasia. Autoantibodies to parathyroid and adrenal glands and type I interferons (IFN) are hallmarks of APS I, which results from mutations in the autoimmune regulator (AIRE) gene. We wished to study clinical, immunological and genetic features of APS I in Hungarian patients, and to correlate anti-IFN-omega serum concentration with APS I and other multi-organ autoimmune diseases. DESIGN: Detailed analysis of patients with APS I and multi-organ autoimmune diseases. PATIENTS: Seven patients with APS I and 11 patients with multi-organ autoimmune diseases were studied. MEASUREMENTS: Mutational analysis was performed by bidirectional sequencing of AIRE. Antibodies against IFN-omega and endocrine organ-specific autoantigens were studied with radioimmunoassay. RFLP was performed by digestion of DNA with Hin6I restriction enzyme. RESULTS: AIRE sequence analysis revealed homozygous c.769C>T mutations in three patients and compound heterozygous sequence variants (c.769C>T/c.44_66dup26bp; c.769C>T/c.965_977del13bp; c.769C>T/c.1344delC) in four patients with APS I. All the six live patients tested had markedly elevated IFN-omega antibodies, which were not found in heterozygous siblings or parents. One of the identified patients was negative for antibodies against IFN-omega at 6 weeks of age, but became positive at 7 months. At age 1, he is still without symptoms of the disease. In contrast to patients with APS I, no AIRE mutation or elevation of IFN-omega antibodies were detected in patients with multi-organ autoimmune diseases. CONCLUSION: This is the first overview of patients diagnosed with APS I in Hungary. A novel c.1344delC mutation in AIRE was detected. Anti-IFN-omega antibodies seem to appear very early in life and are helpful to differentiate APS I from other multi-organ autoimmune diseases.


Subject(s)
Autoantibodies/immunology , Interferon Type I/immunology , Mutation , Transcription Factors/genetics , Adolescent , Adult , Age Factors , Aged , Base Sequence , Child , DNA Mutational Analysis , Family Health , Female , Humans , Infant , Male , Middle Aged , Pedigree , Polyendocrinopathies, Autoimmune/genetics , Polyendocrinopathies, Autoimmune/immunology , Polyendocrinopathies, Autoimmune/pathology , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Radioimmunoassay , Young Adult , AIRE Protein
20.
Inflamm Res ; 59(2): 159-64, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19757086

ABSTRACT

OBJECTIVE: We investigated the association between systemic lupus erythematosus (SLE) and polymorphisms of interleukin-23 receptor (IL23R) gene, which was recently found to be associated with autoimmune diseases, including Crohn's disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis. SUBJECTS: We analysed 383 SLE patients and 253 controls for rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, 11209026, rs10489629, rs7517847 and rs7530511 variants. METHODS: The analysis was carried out using PCR-RFLP methods. Logistic regression analysis was used to compare the genotype distributions of the polymorphisms and haplotypes between the SLE patients and healthy controls. RESULTS: We observed no significant difference of the examined variants between the patient and control groups. CONCLUSIONS: Our results suggest that neither single nucleotide variants nor haplotypes of IL23R indicate susceptibility to developing SLE in the Hungarian population.


Subject(s)
Lupus Erythematosus, Systemic/ethnology , Lupus Erythematosus, Systemic/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Interleukin/genetics , Adult , Alleles , Case-Control Studies , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Genotype , Haplotypes/genetics , Humans , Hungary , Middle Aged
SELECTION OF CITATIONS
SEARCH DETAIL