Macrophage colony-stimulating factor receptor/CD115+ non-classical monocytes are expanded in systemic lupus erythematosus and associated with lupus nephritis.

OBJECTIVE: In systemic lupus erythematosus (SLE), the non-classical monocyte compartment is expanded, but its phenotype and association with clinical disease manifestations have not been explored. METHOD: Monocyte subsets from 39 SLE patients, 32 healthy age-matched controls, and 16 patients from a disease control (autoimmune connective tissue disease other than SLE) were determined based on CD14 and CD16 surface expression. Cell surface expression of the receptors for macrophage colony-stimulating factor (M-CSF) (CD115) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (CD116), as well as 6-Sulpho LacNAc (slan), were analysed by flow cytometry. The association of monocyte populations with disease manifestations, disease activity markers, and current medication of each patient was analysed by chart review. RESULTS: Non-classical monocytes displayed a cell-type specific signature of high M-CSF receptor CD115 and low GM-CSF receptor CD116 expression that separated them from the other two monocyte subsets. In healthy individuals, the M-CSF receptor on non-classical monocytes was an age-dependent surface marker, with lower expression in young adults. However, SLE monocytes were characterized by a marked expansion of M-CSF receptor/CD115+ non-classical monocytes in patients of all ages. The expanded population of M-CSF receptor/CD115+ non-classical monocytes was associated with lupus nephritis but not with disease activity, and coexpressed slan. CONCLUSION: The non-classical monocyte subset in SLE is characterized by an expansion of M-CSF receptor/CD115+ cells that are associated with lupus nephritis and coexpress slan.

[Salivary gland ultrasound or biopsy? : Comparison of methods based on case examples]. / Speicheldrüsenultraschall oder Biopsie? : Methoden im Vergleich anhand von Fallbeispielen.

BACKGROUND: Ultrasound examination of the salivary glands (SG) is a quick and noninvasive method to detect and semiquantitatively estimate typical changes in the large SG in Sjögren's syndrome (SS). The differential diagnosis of SS is difficult because several diseases and adverse effects of treatment have a similar clinical picture as SS with sicca syndrome and can even induce alterations in the SG (mimic diseases). Hence, for a long time an SG biopsy was regarded as the diagnostic procedure of choice, especially in SS­A negative patients, whereas the significance of SD sonography is still controversially discussed. OBJECTIVE: Comparison of typical and atypical changes for SS in the salivary glands in ultrasound and associated histological sections. MATERIAL AND METHODS: This article describes six patient cases with antibody positive or negative SS with and without typical SS ultrasound patterns, SS-associated lymphoma, sarcoidosis and IgG4-associated disease. The findings of the sonographic examination of the parotid glands and the associated histology of the SD are explained and put into context. RESULTS: The SSA antibody positive patients with SS show a typical sonographic pattern with hypoechoic foci, especially if the disease has been present for a long time. This pattern can help support the diagnosis of SS. The ultrasound patterns of the mimic diseases sometimes differ significantly from the typical patterns of pSS. The histological examination of the SG helps to corroborate the diagnosis but low histological focus scores, in particular, require a critical synopsis of the clinical, serological and imaging findings. CONCLUSION: Both salivary gland ultrasound and the histological examination of SG biopsies are justified in the diagnostics and differential diagnosis of SS and sicca syndrome.

The ageing joint-standard age- and sex-related values of bone erosions and osteophytes in the hand joints of healthy individuals.

OBJECTIVE: To analyze the age-related changes of the physiological hand joint architecture. METHOD: To address this concept, healthy individuals (each 10 women and 10 men in six different age decades spanning from 21 to 80 years) were recruited through a field campaign, investigated for the absence of rheumatic diseases and other comorbidities and received high-resolution quantitative computed tomography (HR-pQCT) examination of the hand joints. Number and extent of erosions and osteophytes were quantified across the ages and different sexes. RESULTS: Bone erosions [median (Q1-Q3), 1 (0-2)] and osteophytes [2 (1-4)] were found in healthy women and men with no significant sex differences. Structural changes however accumulated with age: the overall incidence rate ratio (IRR) for the number of erosions and osteophytes per age were 1.04 (95% CI: erosions 1.03-1.06; osteophytes: 1.03-1.05). This means a 4% increase in the number of erosions and osteophytes per year. Using third decade as reference, healthy individuals in the age decades from 50 years had higher IRR for erosion numbers (sixth, seventh, eigth decade: 4.87 (2.20-11.75), 6.81 (3.08-16.46) and 6.92 (3.11-16.79)) compared to younger subjects (fourth, fifth decade: 1.80 (0.69-4.87), 1.53 (0.59-4.10)). The IRRs of osteophytes also indicate a gradual increase after the fifth decade, with IRRs of 2.32 (1.32-4.17), 4.17 (2.38-7.49) and 6.86 (3.97-12.20) for the sixth, seventh and eigth decades, respectively. CONCLUSIONS: Structural changes in the hand joints of healthy individuals are age dependent. While being rare under 50 years of age, erosions and osteophytes accumulate above the age of 50, suggesting that the threshold between "normal" and "pathological" is shifted with the increase of age.

[Pathogenesis of systemic lupus erythematosus]. / Pathogenese des systemischen Lupus erythematodes.

The causes of diseases and disorders of the immune system, which lead to the development of systemic lupus erythematosus (SLE), are not yet completely understood; however, it is known that there are various mechanisms, which can lead to SLE. The development of the disease is based on an underlying genetic disposition but is first triggered by exposure to environmental factors, such as sunburn, viral infections or vitamin D deficiency. Disease flares can also be triggered by environmental factors. Many disease manifestations are caused by pathogenic autoantibodies; hence, B­cells and plasma cells play a critical role in the pathogenesis of SLE. This review provides an overview of the most frequent factors leading to the development of SLE and describes the key mechanisms of its pathogenesis.

[High-resolution peripheral quantitative CT (HR-pQCT). New insights into arthritis]. / Hochauflösende periphere quantitative CT (HR-pQCT). Neue Einblicke in die Arthritis.

The detection of periarticular bone lesions is of crucial importance in the diagnosis and treatment monitoring of chronic inflammatory diseases such as, but not limited to, rheumatoid arthritis (RA). High-resolution peripheral quantitative computed tomography (HR-pQCT) was initially developed for the meticulous assessment of bone microstructure with a focus on bone density parameters. With an isotropic voxel size of 82 µm HR-pQCT is, however, also well suited for quantitative evaluation of periarticular bone lesions, such as erosion, osteophytes as well as bone surface changes in arthritis. The present article gives an overview of the manifold possibilities of application of this novel imaging modality and addresses potential benefits of this technique for rheumatology in the future.

[Imaging modalities in psoriatic arthritis]. / Bildgebende Verfahren bei Psoriasisarthritis.

This review presents an overview of the range of imaging modalities used in the diagnostic evaluation of patients with psoriatic arthritis (PsA). Conventional radiography is used to detect structural changes of the joints and tendon attachments. These changes occur late in the course of PsA hence conventional radiography contributes little to the early detection of PsA; however, the detection of periosteal proliferations on radiographs allows a relatively specific diagnosis of PsA. Skeletal scintigraphy and computed tomography are rarely used in PsA. Arthrosonography (ultrasound of the joints) is gaining increasing importance in the early identification of inflammatory soft tissue signs of PsA in the peripheral joints. Sonography enables early detection of synovitis and tenosynovitis as well as superficial erosions and also inflammatory processes of the tendon attachments. Magnetic resonance imaging (MRI) is indispensable for identifying possible involvement of the axial skeleton. Moreover, it allows good visualization of periostitis and arthritis. High resolution microcomputed tomography is an interesting novel diagnostic tool which allows highly sensitive evaluation of the bone structure and can detect very tiny bone lesions where typical signs of PsA are omega-shaped erosions and small corona-like spikes. Another interesting new diagnostic technique is fluorescence optical imaging (FOI) with the Xiralite system which is highly sensitive for detecting inflammatory processes of the hands.

[Psoriatric arthritis - a permanent challenge for rheumatologists and patients: part 2: imaging diagnostics, classification and therapy]. / Psoriasisarthritis - eine bleibende Herausforderung für Rheumatologen und Patienten: Teil 2: Bildgebende Diagnostik, Klassifikation, Therapie.

In recent years a considerable number of imaging techniques have been used to demonstrate the onset and progression of arthritis-related changes in psoriatric arthritis (PsA). Moreover the identification of new immunological pathways has resulted in a substantial improvement of available therapies for PsA increasing the chance for the individual to receive effective treatment. Although an all-embracing disease activity score is still lacking, there is a variety of symptom-related tools to adequately reflect the course of disease and to evaluate the corresponding treatment success. This manuscript aims to give an overview of the latest corresponding knowledge with respect to PsA.

[Psoriatic arthritis : a permanent challenge for rheumatologists and patients--Part 1: epidemiology, pathogenesis and clinical course]. / Psoriasisarthritis : Eine bleibende Herausforderung für Rheumatologen und Patienten - Teil 1: Epidemiologie, Pathogenese und Klinik.

Psoriatic arthritis is still one of the big challenges in rheumatology due to the great variety of symptoms. Treatment frequently requires an interdisciplinary collaboration of general practitioners, dermatologists and rheumatologists who are able to recognize the onset of disease early by means of classification criteria and new imaging techniques followed by the implementation of appropriate antirheumatic treatment. During recent years new immunological pathways have been discovered leading to an increasing number of potential therapies, which increases the chance to find effective individualized treatment. However, tracking back the onset of the disease to specific causes is still a challenge which is made even more complex due to the absence of specific serum parameters.

Photopheresis with UV-A light and 8-methoxypsoralen leads to cell death and to release of blebs with anti-inflammatory phenotype in activated and non-activated lymphocytes.

BACKGROUND: Extracorporeal photopheresis is a therapy for treatment of autoimmune diseases, cutaneous T-cell lymphoma, organ graft rejection as well as graft-versus-host diseases. The exact mechanism how the combination of 8-methoxypsoralen plus UV-A irradiation (PUVA) acts is still unclear. We investigated the cell death of activated and non-activated lymphocytes after PUVA treatment as well as the rate of released blebs and their antigen composition. RESULTS: In presence of 8-MOP, UV-A light highly significantly increased the cell death of activated lymphocytes. The same was observed to a lesser extent in non-activated cells. Blebs derived from activated lymphocytes after PUVA treatment showed the highest surface exposition of phosphatidylserine. These blebs also displayed a high exposure of the antigens CD5 and CD8 as well as a low exposure of CD28 and CD86. CONCLUSION: PUVA treatment exerts anti-inflammatory effects by inducing apoptosis and apoptotic cell-derived blebs with immune suppressive surface composition.