Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis.

Normalizing bone metabolism is a challenge in rheumatoid arthritis (RA). Studies in mice suggest that anti-citrullinated protein antibodies (ACPAs) can trigger osteoclast activation and bone resorption in the bone marrow. However, data on the presence and role of ACPAs in human bone marrow are scarce. We investigated whether ACPAs can contribute to osteoclast activation and bone erosion in RA bone marrow. Anti-cyclic citrullinated peptide antibodies (anti-CCP Abs), osteoclast activation indicators-the tartrate-resistant acid phosphatase 5b (TRAP5b) and cathepsin K, and bone degradation marker-C-terminal telopeptide of type I collagen (CTX-I) were measured in the bone marrow and peripheral blood of RA patients using ELISAs. We found that ACPAs present in RA bone marrow was associated with increased amounts of TRAP5b, cathepsin K and CTX-I in this location. Levels of IL-8, the key mediator of anti-citrullinated protein antibody (ACPA)-induced bone resorption, were also elevated in bone marrow containing anti-CCP Abs and positively correlated with TRAP5b and cathepsin K concentrations. Higher levels of TRAP5b, cathepsin K, CTX-I and IL-8 in bone marrow compared to peripheral blood indicate local generation of these molecules. Our results complement data from animal studies and highlight the relevance of ACPAs and bone marrow in bone resorption in RA.

Distributional Patterns of Aquatic Empididae (Diptera) along an Elevational Diversity Gradient in a Low Mountain Range: An Example from Central Europe.

The two subfamilies Hemerodromiinae and Clinocerinae, also known as aquatic dance flies, are a group of small predatory insects occurring mainly in mountainous areas and the northern temperate. However, very little is known about distribution patterns for most of the species. Habitat preferences for 40 aquatic empidid species were analysed in the Pieniny Mts., Poland. Forty-six sampling sites from a major part of this relatively low mountain massif (400-770 m) were chosen, for which 17 micro and macrohabitat environmental variables were measured including both abiotic (altitude, stream mean width and depth, and shading) and biotic factors (13 dominant plant communities). Here we show that numerous studied aquatic Empididae were characterized by unique habitat preferences and were restricted to the foothills or the lower montane zone with only a few species characterized by wider elevational distribution. Chelifera pectinicauda, C. flavella, C. subangusta and Phyllodromia melanocephala (Hemerodromiinae), and Clinocera appendiculata, C. fontinalis, C. wesmaeli, Dolichocephala guttata, D. oblongoguttata, Kowarzia plectrum, Wiedemannia jazdzewskii, and W. thienemanni (Clinocerinae) were clearly associated with the highest altitudes and shaded areas while W. bistigma, W. lamellata, W. phantasma, and W. tricuspidata (Clinocerinae) were clearly associated with the lower elevated, wider stream valleys overgrown by willow brakes. Species richness and diversity decreased along elevational gradient with the hump-shaped diversity pattern noted for the subfamily Clinocerinae. The altitude, size of river/stream as well as the type of plant community were found as the most important factors in the distribution of the studied aquatic empidid species. The present study is the first one focused on elevational diversity gradient and habitat preferences of Hemerodromiinae and Clinocerinae of central Europe, and one of only a few in the world.

First detailed records of water mite larvae (Hydrachnidia: Hydrovolzidae, Hydryphantidae) parasitizing empidid flies (Diptera: Empididae: Clinocerinae).

Five species of the subfamily Clinocerinae from the Tatra Mountains (S Poland) were observed to be parasitized by larval water mites. Two of them: Kowarzia plectrum Mik, 1880 and Clinocera storchi Mik, 1880 are recorded from this massif for the first time. In addition, C. storchi, is new for Polish fauna. The most infected species was Clinocera appendiculata Zetterstedt, 1838, following by Wiedemannia mikiana (Bezzi, 1899), Clinocera storchi Mik, 1880, Kowarzia plectrum Mik, 1880 and Wiedemannia jazdzewski Niesiolowski, 1987. The highest number of hosts occurred in the case of Panisopsis curvifrons (Walter, 1907) with five host species, following by both Hydrovolzia placophora (Monti, 1905) and Protzia eximia (Protz, 1896) with one species each. In the case of Clinocera appendiculata more parasites were recorded on males than on females and in C. storchi more parasites were recorded on females. The abdomen of the hosts was the most often chosen by water mites larvae.

Rheumatoid arthritis bone marrow environment supports Th17 response.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic, autoimmune disease leading to joint destruction and ultimately disability. Bone marrow (BM) is an important compartment in RA, where pathological processes from "outside the joint" can occur. IL-17 is a cytokine that exerts proinflammatory effects and participates in the process of bone destruction. It is believed that IL-17 is involved in pathogenesis of RA. However, little is known about the biology of this cytokine in BM. In the present study we investigated Th17-related cytokines in RA BM. METHODS: BM samples were obtained from RA and osteoarthritis (OA) patients during total hip replacement surgery. Levels of IL-17AF, IL-17AA, IL-17FF, IL-1ß, IL-6, IL-23, TGF-ß and CCL20 in BM plasma were determined by specific enzyme-linked immunosorbent assay tests. Percentage of IL-17-producing cells in BM was evaluated by flow cytometry. The effect of IL-15 stimulation on IL-17 production by BM mononuclear cells was examined in vitro. RESULTS: Increased levels of IL-17AF were observed in BM plasma of RA patients in comparison to OA patients. Increased concentrations of IL-1ß, IL-6 and CCL20 were observed in RA compared to OA BM plasma. Concordant with these findings, significantly increased percentages of CD3+CD4+IL-17+ and CD3+CD4+IL-17+IFN-γ+ cells were present in RA BM in comparison to OA BM samples. Finally, abundant in RA BM, IL-15 increased IL-17 production by cultured BM mononuclear cells. CONCLUSIONS: In the course of RA, the BM microenvironment can promote the development of Th17 cell responses and overproduction of IL-17AF that may lead to increased inflammation and tissue destruction in RA BM.

Complex diagnostics of common conditions of the motor organ of the developmental age.

Some muscular and osteoarticular diseases pose serious diagnostic problems, e.g. subsequent recurrent or persistent conditions of isolated pain in the extremities, most frequently - in the lower extremities, especially knee joints, and isolated pain in the back, usually in the lumbosacral spine. They are often accompanied by gait abnormalities. The paper herein presents a complex differential diagnosis of these conditions, the presented diseases that can cause them, and the role of the family doctor, paediatrician, orthopaedist, and rheumatologist in the diagnosis. A detailed history of the presented complaints, accurate physical examination, plus extensive biochemical and immunological diagnostics, and microbiological and imaging techniques usually allow a diagnosis to be made. Attention was paid to the sequence of imaging procedures conducted in the differential diagnosis of pains of the extremities and the spine and not to overuse procedures that involve exposure to ionising radiation.

Tophi - surgical treatment.

Gout is an inflammatory joint disease associated with deposition of monosodium urate crystals in the bones forming the joints, in periarticular tissues and in other organs. The disease is one of the most frequent causes of disability. This paper presents the case of a 57-year-old male patient treated for generalised gout. A "clinical mask" suggesting another disease was the cause of making the correct diagnosis only six years after the occurrence of the first manifestations. The patient, with high values of inflammatory markers, severe pain and advanced joint destruction, was given an aggressive anti-inflammatory treatment. The unsatisfactory effect of the conservative treatment forced the authors to perform surgical resection of the gouty nodules in the hands. After several operations the function of the hand joints operated on, appearance of the hands and the quality of the patient's life improved significantly.

Different expression of chemokines in rheumatoid arthritis and osteoarthritis bone marrow.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. In addition to involvement of the joints, there is growing evidence that inflammatory/autoimmune processes take place in bone marrow, beginning the disease onset. Activated T and B cells accumulate in bone marrow, where also effective antigen presentation takes place. An increased number of activated T cells was observed in RA in comparison to osteoarthritis (OA) bone marrow. In the present study we analyzed the levels of chemokines that may be responsible for accumulation/retention of T-cells in the bone marrow of RA and OA patients. MATERIAL AND METHODS: Bone marrow samples were obtained from RA and OA patients during total hip replacement surgery, and bone marrow plasma was obtained by gradient centrifugation. Levels of the chemokines CX3CL1, CCL5, CCL2, CXCL12 and CXCL1 were measured in bone marrow plasma by specific ELISAs. Comparison between the groups of patients and statistical significance were analyzed by the two-tailed Mann-Whitney U test. RESULTS: Increased levels of CX3CL1 (818 ±431 pg/ml vs. 502 ±131 pg/ml, p < 0.0007) and CCL5 (5967 ±1680 pg/ml vs. 4878 ±2360 pg/ml, p < 0.05) respectively in bone marrow plasma from RA in comparison with OA patients were observed. In contrast, similar levels of CCL2, CXCL12 and CXCL1 in RA and OA bone marrow suggest that these cytokines do not play a significant role in the observed T cell accumulation in RA bone marrow. CONCLUSIONS: CX3CL1 and CCL5 overproduced in RA bone marrow may contribute to the accumulation of T cells observed in RA bone marrow.

Resource specialists lead local insect community turnover associated with temperature - analysis of an 18-year full-seasonal record of moths and beetles.

Insect responses to recent climate change are well documented, but the role of resource specialization in determining species vulnerability remains poorly understood. Uncovering local ecological effects of temperature change with high-quality, standardized data provides an important first opportunity for predictions about responses of resource specialists, and long-term time series are essential in revealing these responses. Here, we investigate temperature-related changes in local insect communities, using a sampling site with more than a quarter-million records from two decades (1992-2009) of full-season, quantitative light trapping of 1543 species of moths and beetles. We investigated annual as well as long-term changes in fauna composition, abundance and phenology in a climate-related context using species temperature affinities and local temperature data. Finally, we explored these local changes in the context of dietary specialization. Across both moths and beetles, temperature affinity of specialists increased through net gain of hot-dwelling species and net loss of cold-dwelling species. The climate-related composition of generalists remained constant over time. We observed an increase in species richness of both groups. Furthermore, we observed divergent phenological responses between cold- and hot-dwelling species, advancing and delaying their relative abundance, respectively. Phenological advances were particularly pronounced in cold-adapted specialists. Our results suggest an important role of resource specialization in explaining the compositional and phenological responses of insect communities to local temperature increases. We propose that resource specialists in particular are affected by local temperature increase, leading to the distinct temperature-mediated turnover seen for this group. We suggest that the observed increase in species number could have been facilitated by dissimilar utilization of an expanded growing season by cold- and hot-adapted species, as indicated by their oppositely directed phenological responses. An especially pronounced advancement of cold-adapted specialists suggests that such phenological advances might help minimize further temperature-induced loss of resource specialists. Although limited to a single study site, our results suggest several local changes in the insect fauna in concordance with expected change of larger-scale temperature increases.

Pain associated with the musculoskeletal system in children from Warsaw schools.

OBJECTIVE: To assess the prevalence of pain in the musculoskeletal system and possible reasons for these complaints among early age children from Warsaw schools. MATERIAL AND METHODS: The study was conducted in 34 randomly selected primary schools in Warsaw in 2011. 2748 survey-questionnaires were given to parents or legal guardians by children. Of these, 1509 surveys were subject to a final analysis. The survey included 66 questions regarding, among other things, pain in the musculoskeletal system in children. Additionally, there were questions about possibly occurring diseases, any postural defects, significant obesity, as well as effects of these complaints on the child's physical activity. Survey data regarded 6-7-year-old children. RESULTS: In the group of 1509 respondents, 242 children (16%) complained about pain in the musculoskeletal system. Pain was located most frequently in the knee joints, and more rarely in the spine and joints in the upper extremities. In the group of children who complained about pain, moderate physical activity was statistically significantly limited. According to parents, physicians did not diagnose any medical conditions in 106 children. Joint disease was diagnosed in 33 children. Postural defects were diagnosed in 589 children. In 123 children complaining about pain at least one postural defect was diagnosed. Such defects were diagnosed statistically significantly more rarely (p = 0.011) in 1234 children who did not complain about pain (460 children). Platypodia or other foot deformation was observed in 25% of these children, spinal curvature in 12%, abnormal knee joint position in 11% and uneven hip position in 2% children. Of note, 17% of all children were significantly overweight. In overweight children the prevalence of pain, especially in the knee joints and feet, was significantly higher. CONCLUSIONS: This study aims to underline the problem of musculoskeletal pain in early-age children which limits their physical activity. Also the authors draw attention to the issue of postural defects in a large group of school children. This issue undoubtedly requires more attention and a plan how to create more effective methods of prevention.

Syndromes with chronic non-bacterial osteomyelitis in the spine.

Chronic non-bacterial osteomyelitis (CNO) has been known for over of 40 years. It is an underrecognized entity due to the low number of described cases and poor propagation awareness of the problem. Chronic non-bacterial osteomyelitis is usually confused with infectious spondylodiscitis or malignant lesions, both primary and metastatic. Failing to consider CNO as one of possible lesions of the spine among an array of differential diagnoses may lead to a prolonged ineffective treatment increasing treatment-related morbidity. In this paper the authors describe these two syndromes, with a possible autoimmune background - chronic recurrent multifocal osteomyelitis (CRMO) and SAPHO syndrome - that include CNO being among the manifestations. The authors present the spinal symptomatology of CNO for both syndromes published so far to help spine clinicians organize the information for better usage in everyday clinical practice.

Bone graft incorporation after revision hip arthroplasty in patients with rheumatoid arthritis: seventy eight revisions using bone allografts with or without metal reinforcements.

PURPOSE: The aim of the study was to assess bone graft incorporation after revision hip arthroplasty in patients with rheumatoid arthritis (RA). METHODS: We report an acetabular reconstruction using impacted, morselized, frozen, radiation sterilized bone allografts in 71 patients suffering from RA. There were sixty-six women and five men at a mean age of 57.5 years. Reconstruction was performed in 78 revision total hip arthroplasties (THAs) for aseptic loosening of acetabular component. The mean follow-up was five years and four months. In 38 cases, a revision was done with use of reinforcement devices. RESULTS: In four revised hips (10 %) without reinforcement implants, resorption of the allografts was noticed. All Mueller rings and 50 % of unscrews cages (Link, Howmedica) were revised because of aseptic loosening and bone graft resorption. In all of 17 hips with the Burch-Schneider cage, no measurable migration or bone allografts resorption occurred. There were no major general complications. CONCLUSIONS: Acetabular reconstruction with use of morselized, frozen, radiation sterilized bone allografts and the Burch-Schneider cage can be highly successful in managing massive deficiency of acetabular bone stock in revision hip arthroplasty in RA patients.

[Juvenile spondyloarthropaties]. / Mlodziencze spondyloartropatie.

Epidemiologic, clinical, and genetic studies provide grounds for differentiation of juvenile spondyloarthropathies from other rheumatic diseases. The prevalence of spondyloarthropathies among whites is estimated at 0.7 to 1.2% and the female-to-male ratio is 1:2.5. The current classification of clinically defined and undefined forms of juvenile spondyloarthropathies is presented together with their diagnostic criteria and treatment.