Osteopontin Gene Polymorphisms rs1126616 C>T and rs1126772 A>G are Associated with Atopic Dermatitis in Polish Population.

PURPOSE: Atopic dermatitis (AD) is a chronic, relapsing inflammatory disease, caused by environmental and genetic factors, which lead to immunological abnormalities. Osteopontin (OPN), also named secreted phosphoprotein 1 (SPP1), is a protein involved in the pathogenesis of numerous autoimmune and inflammatory conditions. However, its role in AD has not been fully elucidated. Therefore, we aim to gain an insight into the role of OPN in AD pathogenesis through investigating its gene single nucleotide polymorphisms (SNPs) and their possible associations with disease clinical features. PATIENTS AND METHODS: A total of 182 Caucasian participants (45 AD patients and 137 gender- and age-matched controls) were studied. Genomic DNA was isolated from peripheral blood samples. Genotyping for the rs1126616 C>T, rs1126772 A>G, rs9138 A>C, and rs3841116 T>G SNPs was performed by real time polymerase chain reaction (RT-PCR). RESULTS: The frequency of the minor TT genotype and the T allele of rs1126616 C>T was higher in AD patients compared to controls (P = 0.019, OD = 4.86, 95% CI = 1.46-16.20, and P = 0.047, OR = 1.77, 95% CI = 1.04-3.00, respectively) and was associated with the higher prevalence of asthma (P = 0.017, OR = 3.73, 95% CI = 0.71-19.67, and P = 0.004, OR = 3.96, 95% CI = 1.53-10.25, respectively). Likewise, the minor GG genotype and the G allele of rs1126772 A>G were more frequent in AD patients (P = 0.026, OR = 3.27, 95% CI = 1.29-8.33, and P = 0.013, OR = 1.94, 95% CI = 1.18-3.21, respectively) and were associated with the increased incidence of asthma (P = 0.016, OR = 5.06, 95% CI = 1.14-22.49, and P = 0.002, OR = 4.40, 95% CI = 1.71-11.35, respectively). Furthermore, haplotype frequency estimation determined the four-loci haplotype TGCT, as a significant risk factor for AD compared to controls (P = 0.031, OR = 9.48, 95% CI = 1.23-71.91). CONCLUSION: Our results suggest that the variation in the OPN gene might be associated with AD and increased incidence of asthma in Caucasians. Further studies should be conducted to look into the possible role of OPN as a biomarker for AD.

The Pancreatitis, Panniculitis, and Polyarthritis (PPP) Syndrome: Subcutaneous Nodular Fat Necrosis, a Cutaneous Marker of Pancreatic Neoplasia.

The pancreatitis, panniculitis, polyarthritis (PPP) syndrome is a rare skin, joint, and pancreatic disorder, also known as subcutaneous nodular fat necrosis. It results from obstruction of pancreatic ducts with direct secretion of pancreatic enzymes into the bloodstream, causing extra pancreatic fat necrosis with subcutaneous tissue and joint inflammation. It is usually a cutaneous sign of pancreatic cancer or pancreatitis. To our knowledge, this is the first case associated with a pancreatic pseudotumor. We describe a 59-year-old man initially presenting with numerous painful erythematous subcutaneous nodules due to a fibrous pancreatic pseudotumor and its extreme dermatologic disease, resulting in necrosis of the shin and foot so severe that an amputation of the lower leg above the knee was required, a complication not previously described, to our knowledge. We emphasize that PPP syndrome is a cutaneous marker of internal malignancy, most often of pancreatic cancer or pancreatitis, but in this case of a rare pancreatic pseudotumor.

The preliminary association study of osteopontin 707 C/T polymorphism with systemic lupus erythematosus in a Polish population.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease caused by genetic, environmental, and still unknown factors which lead to deregulation of the immune system. Osteopontin (OPN) is a multifunctional glycoprotein, expressed in various cell types, and found to play key roles in immunity. OPN and variants of the OPN gene are involved in inflammatory conditions, however, their role in SLE are controversial. AIM: To investigate the frequency of single nucleotide polymorphism (SNP) rs1126616 (707 C/T) variants in the OPN gene and its associations with SLE manifestations in Polish patients. MATERIAL AND METHODS: The study population consisted of 83 SLE patients and 100 gender-, age- and ethnically matched healthy controls. DNA was extracted from whole blood samples using the standard procedure. Genotyping was performed by real-time polymerase chain reaction (RT-PCR). The association between clinical features of SLE and 707 C/T genotypes was determined. RESULTS: The mutant (CT, TT) genotypes were observed more frequently than the wild-type (CC) genotype in SLE patients compared to controls (p = 0.037). However, no association between 707 C/T variants and SLE clinical manifestations or laboratory parameters was found. CONCLUSIONS: The present data suggest that CT and TT genotypes of OPN 707 C/T SNP are associated with a higher SLE risk, but do not affect the clinical course of the disease in the Polish population.

Methotrexate use and NAD+/NADH metabolism in psoriatic keratinocytes.

Methotrexate inhibits tetrahydrofolic acid production and influences mitochondrial oxygen uptake and activity of several enzymes in the respiratory chain reactions, which utilize nicotinamide adenine dinucleotide-linked (NAD-linked) substrates. Hyperproliferation of keratinocytes in psoriasis requires oxidative phosphorylation, in which the reduced form of nicotinamide adenine dinucleotide (NADH) is an electron donor. One hypothesis links increased cellular metabolism to the increased NADH/NAD+ ratio; as expected, the topical application of NAD+ (oxidized form of nicotinamide-adenine dinucleotide) resulted in a clinical improvement of psoriatic lesions in one study. Nevertheless, another report revealed reduced fluorescence of NADH in psoriatic plaques. The biological activity of NADH is not limited only to serving as the electron donor. It was also found to regulate gene transcription.

The role of endocan and selected pro-inflammatory cytokines in systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a multisystem inflammatory autoimmune disease with a wide spectrum of clinical manifestations. Cytokines such as interleukin-1 (IL-1) and tumour necrosis factor α (TNF-α) are involved in its pathogenesis. Endocan is a novel marker of endothelial dysfunction and is likely to be engaged in proinflammatory processes in SLE. AIM: To determine whether endocan serum concentration in SLE patients vary from healthy controls. MATERIAL AND METHODS: The study included 36 patients with SLE. SLEDAI-2K score was used to assess disease activity. The control group comprised 23 healthy volunteers. ELISA kits were used to assess serum concentrations of endocan, IL-1ß, TNF-α, vascular endothelial growth factor (VEGF) and high-sensitivity C reactive protein (hs-CRP). RESULTS: The serum concentration of endocan was significantly higher (p < 0.001) in the SLE group than in healthy individuals. A positive correlation was found between serum levels of endocan and IL-1ß (r = 0.47, p < 0.05). Active SLE patients (SLEDAI-2K score above 6 points) with an elevated total cholesterol level (above 5.17 mmol/l) were found to have VEGF concentration higher than those with a normal cholesterol level (p < 0.03). No other relevant relationships were found between the serum concentration of endocan, other laboratory parameters, anthropometric features, activity and duration of SLE. CONCLUSIONS: A higher serum level of endocan in SLE patients indicates its possible role in the pathogenesis of the disease and reflects endothelial dysfunction. Our findings indicate that endocan could serve as a potential marker of endothelial dysfunction in SLE.

The impact of medium dose UVA1 phototherapy on pruritus, DLQI and SCORAD index in patients with atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is featured by pruritus, which causes diminished quality of life. Little clinical data exists concerning the use, efficacy and side effects of UVA1 phototherapy in AD patients. AIM: To determine the effectiveness of medium-dose UVA1 phototherapy in AD treatment. MATERIAL AND METHODS: Thirty-six patients with AD were irradiated with medium-dose UVA1 (45 J/cm2) as monotherapy for 4 weeks for a total of 20 sessions (daily irradiations during weekdays only). Clinical status was evaluated with the visual analogue scale for pruritus, Dermatology Life Quality Index (DLQI) for evaluating general well-being and the SCORAD index. All parameters were measured twice: before and after phototherapy. RESULTS: UVA1 phototherapy resulted in a significant (p < 0.001) decrease in pruritus, improvement in DLQI (p < 0.001) and SCORAD (p < 0.001). Before phototherapy, the intensity of pruritus and SCORAD index correlated with DLQI (r = 0.34, p < 0.05 and r = 0.61, p < 0.05, respectively). Similarly, after irradiation, pruritus correlated with DLQI, and SCORAD index correlated with DLQI (r = 0.51, p < 0.05 and r = 0.55, p < 0.05, respectively). No severe adverse effects were noted during the study. CONCLUSIONS: Phototherapy with medium-dose UVA1 irradiation exerts a significant antipruritic effect, decreases the severity of the disease and improves the quality of life of AD patients. This technique can therefore be used as a safe and effective treatment method.

Serum concentrations of IL-17A, IL-17B, IL-17E and IL-17F in patients with systemic sclerosis.

INTRODUCTION: Immune system activation, microvascular abnormalities and extracellular matrix deposition in tissues play roles in systemic sclerosis (SSc). Th17 cells producing interleukin (IL)-17 are involved in the pathogenesis of many autoimmune-mediated inflammatory diseases; however, the role of IL-17 in SSc remains unclear. MATERIAL AND METHODS: The concentrations of IL-17A, IL-17B, IL-17E, and IL-17F in the serum of patients with SSc and in the healthy control group were assessed with regard to type of the disease - whether limited (lSSc) or diffuse (dSSc) - and symptoms. RESULTS: No difference was found between patients with SSc and the control group as regards the serum concentration of IL-17A. However, IL-17B and IL-17E levels in patients with SSc, and its types diffuse and limited were higher (p < 0.001) compared to the control. The serum level of IL-17F was higher in SSc (p < 0.005) and lSSc (p < 0.05) compared to the control. Serum concentration of IL-17B was elevated in SSc patients with renal abnormalities (p < 0.05) compared to those without. Serum levels of IL-17B correlated with the levels of IL-17E in patients with SSc (r = 0.54, p < 0.05). CONCLUSIONS: Increased synthesis of IL-17B, IL-17E and IL-17F appears to play a role in the pathogenesis of SSc, in contrast to IL-17A. Higher levels of IL-17B and IL-17E are associated with the development of both lSSc and dSSc, whereas IL-17F is associated with lSSc only. Further studies are needed to elucidate their role in the pathogenesis of the disease.

Changes of NADH Fluorescence from the Skin of Patients with Systemic Lupus Erythematosus.

INTRODUCTION: The blood circulation of the skin is an accessible and representative vascular bed for examining the mechanisms of microcirculatory function. Endothelial function is impaired in systemic lupus erythematosus (SLE), which implies disorders in cell metabolism dependent on blood circulation; however, noninvasive monitoring of metabolism at the tissue and cell level is absent in daily clinical practice. OBJECTIVE: The aim of the study was to examine changes of NADH fluorescence from the epidermis of a forearm measured with the flow mediated skin fluorescence (FMSF) technique in patients with SLE and to investigate whether they are associated with clinical manifestation of the disease. MATERIALS AND METHODS: The study enrolled 36 patients with SLE and 34 healthy individuals. Changes of NADH fluorescence were measured using FMSF on the forearm in response to blocking and releasing of blood flow. The results were represented as ischemic (IR max and IR auc) and hyperemic response maximum and area under the curve (HR max and HR auc). RESULTS: IR max, IR auc, HR max, and HR auc were all lower in patients with SLE (p < 0.05) compared with controls. All four parameters were negatively correlated (p < 0.05) with patient age. No difference was found in NADH fluorescence between SLE patients with malar rash, discoid rash, photosensitivity, oral ulcers, nonerosive arthritis, renal disorder, hematologic disorder, or immunologic disorder and those without. No correlation was revealed between the SLEDAI score and NADH fluorescence. CONCLUSION: Changes of NADH fluorescence indicate the reduction in NADH restoration, observed especially during reperfusion, and suggest the occurrence of disorders in the microcirculation of the skin and/or at the mitochondrial level. Such changes of NADH during reperfusion in patients with SLE could be associated with their possible lower sensitivity to hypoxia and possibly with endothelial dysfunction.

Cellulite: a cosmetic or systemic issue? Contemporary views on the etiopathogenesis of cellulite.

Cellulite (also known as gynoid lipodystrophy or orange peel syndrome) is one of the most common lipodystrophy syndromes, which affects millions of post-adolescent women. Cellulite is manifested by topographic disorders of subcutaneous tissue such as nodules, edema, and abnormal fibrosis. It is located mainly on the pelvic area, especially on the buttocks. Its pathogenesis is complexed and unclear. There are several theories about its pathophysiology. Hormonal disorders, endothelial dysfunction and genetic predispositions are taken under consideration.

Contact allergy in the population of patients with chronic inflammatory dermatoses and contact hypersensitivity to corticosteroids.

INTRODUCTION: Clinical studies indicate that contact allergy to glucocorticosteroids (GCS) is not rare and has been increasingly reported over the past decade. Among the risk factors for developing contact hypersensitivity to topical corticosteroids, chronic inflammatory skin diseases and polyvalent contact allergy seem to be most important. AIM: To present the structure of contact allergy in the population of patients with chronic inflammatory dermatoses (CID) and contact hypersensitivity to corticosteroids. MATERIAL AND METHODS: Twenty-seven patients with contact allergy to GCS and chronic inflammatory dermatoses were patch tested with 28 European Baseline Series allergens and 8 corticosteroid allergens. This study group consisted of 5 patients with atopic dermatitis (AD), 15 patients with contact eczema (CE) and 7 with chronic leg eczema (CLE). Nineteen (70.4%) patients were females and 8 (29.6%) were males. RESULTS: In the study group, the most sensitizing non-steroidal allergens were nickel sulfate (51.8%), cobalt chloride (33.3%) and balsam of Peru (29.6%). The most sensitizing corticosteroid allergens were budesonide (77.8%), betamethasone valerate and clobetasol propionate (55.5% each). A total of 77.8% of patients allergic to GCS also showed sensitivity to at least one non-steroidal allergen from the European Baseline Series. CONCLUSIONS: The most important risk factors for developing contact allergy to corticosteroids appear to be chronic inflammatory dermatoses, long disease duration, extended on-and-off topical corticosteroid use, patients presenting two or more positive patch test results and polyvalent contact allergy to metal salts and to other non-steroidal haptens.

Medium dose ultraviolet A1 phototherapy and mRNA expression of interleukin 8, interferon γ, and chemokine receptor 4 in acute skin lesions in atopic dermatitis.

INTRODUCTION: Mechanisms responsible for UVA1 efficacy in atopic dermatitis (AD) are not fully elucidated. AIM: To investigate IL-8, CCR-4, and IFN-γ mRNA expression in AD before and after UVA1, to identify correlations among them, and to determine whether and to what degree mRNA expression is influenced by UVA1. MATERIAL AND METHODS: Twenty-five patients with AD underwent medium dose UVA1-phototherapy at daily dosages of 10, 20, 30, 45, and then continuing 45 J/cm(2) up to 20 days, from Monday to Friday for 4 weeks. Before and after UVA1, biopsies from acute skin lesions were studied using reverse-transcription and RT-PCR. RESULTS: The levels of CCR-4 mRNA correlated with those of IFN-γ, both before and after UVA1 phototherapy (p < 0.05). A significant correlation was found after UVA1 between mRNA levels of IL-8 and IFN-γ (p < 0.05). After UVA1 an increase in IL-8 mRNA expression in comparison to the baseline assessment (p = 0.02) was found, while no significant difference was revealed in the expression of CCR-4 and IFN-γ mRNA. UVA1 improved both SCORAD and severity of AD (p < 0.001). SCORAD and the severity of AD did not correlate with the degree of expression of measured cytokine mRNA, neither before nor after UVA1. CONCLUSIONS: CCR-4 is expressed in parallel with IFN-γ in acute skin lesions of patients with AD both before and after UVA1 phototherapy. UVA1 significantly improves SCORAD index, lessens the severity of AD and increases the expression of IL-8, with no direct effects on other studied molecules.

Contact Hypersensitivity to European Baseline Series and Corticosteroid Series Haptens in a Population of Adult Patients with Contact Eczema.

Contact eczema (CE) is one of the most common skin diseases and is regarded as a reaction pattern. However, the skin can react in the same way to different stimuli, some of which may act together. The golden standard in the diagnosis of allergic contact dermatitis (ACD) is the patch test. Contact allergy to topical corticosteroids is known to be gradually rising, and this represents a significant problem in the treatment of contact eczema. The aim of this study was to evaluate the prevalence of contact allergy to European Baseline Series and Corticosteroid Series haptens in a population of patients with CE. A group of 126 patients with the clinical diagnosis of contact eczema were patch tested with 28 European Baseline Series allergens and 8 corticosteroid allergens in different concentrations and in different media: 80 (64.5%) women and 46 (36.5%) men, mean age 50.4 years. The average duration of CE was 6.9 years. In total, 65 patients (51.6%) demonstrated an allergic reaction to at least one European Baseline Series allergen, and 22 patients (17.4%) to at least one corticosteroid. The most common allergens giving positive results were nickel sulfate (26.2%), cobalt chloride (15.1%), budesonide (14.3%), potassium dichromate (13.5%), and myroxylon pereirae resin (MPR) (11.9%). According our data, the European Baseline Series tests allow the cause of ACD to be identified in over 50% of cases.

Medium-dose ultraviolet A1 phototherapy improves SCORAD index and increases mRNA expression of interleukin-4 without direct effect on human ß defensin-1, interleukin-10, and interleukin-31.

BACKGROUND: Effectiveness of ultraviolet (UV)A1 in flares of atopic dermatitis (AD) is thought to influence the expression of cytokines involved in its pathogenesis. The aim of the study was to investigate whether mRNA expression of human ß defensin-1 (hßD-1) correlates with that of interleukin (IL)-4, IL-10, and IL-31 in skin lesions in AD before and after UVA1 phototherapy, to determine whether UVA1 decreases the expression of the aforementioned mediators, and to confirm whether changes in mRNA expression correspond with the clinical efficacy of UVA1. METHODS: Twenty-five patients with AD underwent medium-dose UVA1 phototherapy. Before and after UVA1, biopsies from acute skin lesions were studied using reverse transcription and real-time polymerase chain reaction. RESULTS: Levels of mRNA hßD-1 correlated with those of IL-10 and IL-31, levels of IL-4 mRNA correlated with those of IL-10 and IL-31, and IL-10 expression correlated with that of IL-31, both before and after UVA1. Phototherapy with UVA1 improved SCORing of Atopic Dermatitis (SCORAD) values, decreased pruritus, and increased expression of IL-4. After UVA1, no difference was found in the mRNA expression of other molecules. The SCORAD index did not correlate with the expression of any examined mRNA either before or after UVA1. CONCLUSIONS: hßD-1, IL-4, IL-10, and IL-31 are expressed in acute skin lesions in AD, and their levels correlate with each other. UVA1 improves SCORAD and pruritus and increases the expression of IL-4 without direct effect on other molecules.

Requirement for vitamin D supplementation in patients using photoprotection: variations in vitamin D levels and bone formation markers.

BACKGROUND: Avoiding sun exposure is obligatory in photodermatoses; however, the need for oral supplementation with vitamin D appears unrecognized. The aim of the study was to investigate the seasonal variation of vitamin D level and bone formation markers in healthy individuals and to compare it with vitamin D status in patients using photoprotection. METHODS: Thirty-four healthy inhabitants of the Lodz region, Poland, a country in central Europe (51° and 52° north latitudes), were examined at the baseline visit within 2 weeks of peak sun exposure during recreational activity on vacation, after 8, and after 16 weeks. The group of patients using photoprotection comprised 104 patients with systemic lupus erythematosus. Serum 25(OH) vitamin D, procollagen type I N-terminal propeptide (PINP), and osteocalcin levels were measured. RESULTS: The serum 25-hydroxyvitamin D concentration was lower and vitamin D deficiency more common in patients using photoprotection than in healthy individuals during the warm and the cold season (P < 0.05). In healthy individuals, vitamin D deficiency was more prevalent after 8 and 16 weeks than at baseline assessment (P < 0.001). PINP level was 39.56 (30.51-53.22) ng/ml, and elevated in 50% of individuals, whereas osteocalcin was 18.88 (13.52-21.33) ng/ml, and within reference range. CONCLUSIONS: Diagnoses of vitamin D deficiency and oral supplementation in patients using photoprotection need to be included in practice. Peak 25-hydroxyvitamin D levels are probably achieved from vitamin D skin synthesis during the summertime and fall over time, starting from August. Elevated levels of PINP appear in line with the process of bone remodeling related to age.

Expression of vascular endothelial growth factor and other cytokines in atopic dermatitis, and correlation with clinical features.

BACKGROUND: Vascular endothelial growth factor (VEGF) was found increased in the stratum corneum of patients with atopic dermatitis (AD). However, its potential pathogenic role(s) in AD needs further clarification. OBJECTIVE: The aim of this study was to determine whether VEGF serum levels correlate with other selected cytokine levels and features of AD. METHODS: VEGF and other cytokine levels were measured in 83 patients with AD and in a control group and then correlated with clinical and laboratory parameters of AD. RESULTS: The mean serum concentrations of VEGF and tumor necrosis factor α were significantly higher in patients with AD than in the control group, whereas the mean interleukin eight serum level was lower. VEGF concentrations correlated with the severity of AD as expressed by SCORAD index and objective SCORAD. CONCLUSION: VEGF could be regarded as a potentially important mediator in the pathogenesis of AD, as VEGF levels correlate somewhat with AD severity.

Medium-dose ultraviolet A1 phototherapy and mRNA expression of TSLP, TARC, IL-5, and IL-13 in acute skin lesions in atopic dermatitis.

BACKGROUND: The mechanisms responsible for the efficacy of ultraviolet A1 (UVA1) in the treatment of atopic dermatitis (AD) are not fully understood. OBJECTIVES: This study was designed to investigate mRNA expression of thymic stromal lymphopoietin (TSLP), thymus- and activation-regulated chemokine (TARC), interleukin-5 (IL-5), and IL-13 in AD before and after UVA1 therapy, to determine correlations among them, and to examine whether UVA1 influences their expression and whether it is associated with UVA1 efficacy. METHODS: Twenty-five patients with AD underwent medium-dose UVA1 phototherapy. Before and after UVA1, biopsies from acute skin lesions were studied using reverse transcription and real-time polymerase chain reaction. RESULTS: Levels of mRNA TSLP correlated with those of TARC, IL-5, and IL-13, and levels of TARC correlated with those of IL-5 and IL-13, both before and after UVA1. Expression of IL-5 correlated with that of IL-13 only before UVA1. SCORAD (SCORing of Atopic Dermatitis) indices correlated with levels of TARC and IL-5 before irradiation. After UVA1, no mRNA level correlated with the SCORAD index. Phototherapy with UVA1 improved SCORAD values (P < 0.001) and increased expression of TARC (P < 0.05) but did not affect mRNA expression of TSLP, IL-5, or IL-13. CONCLUSIONS: Expression levels of the mediators TSLP, TARC, IL-5, and IL-13 in AD are interrelated. Phototherapy with UVA1 improves SCORAD indices and increases expression of TARC but has no direct effects on the expression of other molecules. It is likely that UVA1 also interferes with or acts via intermediators on the link between IL-5 and IL-13.

Viabilidade da mensuração de marcadores de remodelação óssea em mulheres com lúpus eritematoso sistêmico / Feasibility of measurement of bone turnover markers in female patients with systemic lupus erythematosus

Objetivo: Investigar a viabilidade dos marcadores de remodelação óssea (MRO) na avaliação do metabolismo ósseo em pacientes com lúpus eritematoso sistêmico (LES), de acordo com as diretrizes da International Osteoporosis Foundation e da International Federation of Clinical Chemistry and Laboratory Medicine. Métodos: O estudo incluiu 43 pacientes do sexo feminino com LES. Foram medidos os níveis séricos de propeptídeo N-terminal do procolágeno tipo I (PINP), telopeptídeo C-terminal do colágeno tipo I (CTX), osteocalcina, HPT, 25(OH)D, anticorpos anticardiolipina, antidsDNA e antinucleossomo. Resultados: Os níveis de PINP e CTX estavam elevados em pacientes com LES com idade > 45, em comparação com aqueles com idade < 45 anos, embora com significância estatística limítrofe (p = 0,05). Foram encontradas correlações entre os MRO: a mais forte foi entre o PINP e a osteocalcina (τ = 0,69, p < 0,05). Encontrou-se que o PINP e a osteocalcina estão correlacionados com o HPT (τ = 0,3, τ = 0,29, respectivamente, p < 0,05). A idade estava correlacionada com o PINP (τ = 0,23, p < 0,05). Valores elevados de PINP foram encontrados em maior frequência do que valores elevados de osteocalcina ou CTX, tanto em pacientes com idade < 45 (p = 0,001) quanto > 45 (p < 0,001). Não houve diferença estatisticamente significativa nos níveis de PINP, osteocalcina ou CTX com relação à estação do ano, nem em todo o grupo de pacientes com LES, nem naqueles com mais ou menos de 45 anos. O uso prévio de glucocorticoides não esteve associado a diferenças nos MRO. Conclusões: O aumento nos MRO no LES parece refletir predominantemente o padrão de remodelação óssea relacionado com a idade. Pode-se esperar que o PINP aumentado seja o desfecho mais comumente encontrado entre os MRO. É necessário incluir melhores diagnósticos de distúrbios ósseos com MRO, feitos de acordo com as normas internacionais de referência, na abordagem de ...

Objective: To investigate the feasibility of bone turnover markers (BTMs) for the assessment of bone metabolism in patients with systemic lupus erythematosus (SLE), according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. Methods: The study included 43 female SLE patients. Serum pro-collagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), osteocalcin, PTH, 25(OH)D, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were measured. Results: PINP and CTX levels were elevated in SLE patients aged > 45 in comparison to those aged < 45, although with borderline significance (p = 0.05, respectively). Correlations were found between BTMs: the strongest being between PINP and osteocalcin (τ= 0.69, p < 0.05). PINP and osteocalcin were found to be associated with PTH (τ = 0.3, τ = 0.29, respectively, p < 0.05). Age correlated with PINP (τ= 0.23, p < 0.05). Elevated PINP was found more frequently than elevated osteocalcin or CTX, both in patients aged < 45 (p = 0.001) and > 45 (p < 0.001). No significant difference in PINP, osteocalcin or CTX levels was found with respect to season, neither in the entire SLE group, nor in the under-45 or over-45 groups. Previous glucocorticoid treatment was not associated with difference in BTMs. Conclusions: Increased BTMs in SLE appear to predominantly reflect the pattern of bone remodeling related to age. Increased PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of bone disturbances with BTMs performed in accordance with international reference standards need to be included in the approach to SLE patients, in addition to bone mineral density assessment. .

Feasibility of measurement of bone turnover markers in female patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the feasibility of bone turnover markers (BTMs) for the assessment of bone metabolism in patients with systemic lupus erythematosus (SLE), according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. METHODS: The study included 43 female SLE patients. Serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), osteocalcin, PTH, 25(OH)D, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were measured. RESULTS: PINP and CTX levels were elevated in SLE patients aged > 45 in comparison to those aged < 45, although with borderline significance (p = 0.05, respectively). Correlations were found between BTMs: the strongest being between PINP and osteocalcin (τ = 0.69, p < 0.05). PINP and osteocalcin were found to be associated with PTH (τ = 0.3, τ = 0.29, respectively, p < 0.05). Age correlated with PINP (τ = 0.23, p < 0.05). Elevated PINP was found more frequently than elevated osteocalcin or CTX, both in patients aged < 45 (p = 0.001) and > 45 (p < 0.001). No significant difference in PINP, osteocalcin or CTX levels was found with respect to season, neither in the entire SLE group, nor in the under-45 or over-45 groups. Previous glucocorticoid treatment was not associated with difference in BTMs. CONCLUSIONS: Increased BTMs in SLE appear to predominantly reflect the pattern of bone remodeling related to age. Increased PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of bone disturbances with BTMs performed in accordance with international reference standards need to be included in the approach to SLE patients, in addition to bone mineral density assessment.

Cambridge Neuropsychological Test Automated Battery in assessment of cognitive parameters in patients with systemic lupus erythematosus in relation to autoantibody profile.

OBJECTIVES: To relate the cognitive parameters of systemic lupus erythematosus (SLE) patients in remission to their profile of autoantibodies. MATERIAL AND METHODS: The study included 32 patients with SLE in remission, with mild disease activity as indicated by SELENA-SLEDAI < 6. For neuropsychological assessment, the Cambridge Neuropsychological Test Automated Battery (CANTAB) was applied, using motor screening (MOT), big little circle (BLC), paired associated learning (PAL), stockings of Cambridge (SOC), and graded naming tests (GNT). Detection of autoantibodies against dsDNA, nucleosome (aNuc), Sm, and anticardiolipin (aCL: IgG and IgM) was performed with immunoassays. RESULTS: The SLE patients demonstrated standard scores below norms, matched according to age and gender, in the following tests: GNT (-0.87 ±0.85), SOC PSMM (-0.47 ±0.97), PAL (-1.88 ±3.58), and BLC (-0.31 ±1.90). GNT scores under -0.5 were found significantly more frequently in SLE patients, seen in roughly 66% of test subjects. Values for PAL and mean subsequent thinking time of stockings of Cambridge (SOC MSTT) were found to be lower than -0.5 in approximately half of the patients. Mean error of motor screening (MOT ME) was found to negatively correlate with mean latency of motor screening (MOT ML) (r = -0.55). PAL significantly correlated with SOC MSTT (r = 0.38) and with GNT (r = 0.36). Anti-dsDNA antibody level correlated negatively with MOT ME (r = -0.46). Anti-Nuc antibodies correlated with MOT ML (r = 0.41) but negatively correlated with MOT ME (r = -0.58). The levels of anti-Sm, anti-CL IgM and IgG did not correlate significantly with the outcomes of CANTAB. The age of the patients correlated negatively with MOT ME (r = -0.36), positively with BLC (r = 0.53) and negatively with SOC MSTT (r = -0.43). The level of anti-Nuc antibodies correlated with anti-dsDNA level (r = 0.62) and of anti-CL IgM with anti-Sm (r = 0.39) and anti-CL IgG (r = 0.87). CONCLUSIONS: CANTAB reveals a decrease in selected cognitive functions in patients with SLE. ACL IgG and anti-dsDNA antibodies indicated SLE patients prone to develop a decrease in cognitive functions.