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ID PMID Title PublicationDate abstract
29308627 Semaphorin-3A as An Immune Modulator Is Suppressed by MicroRNA-145-5p. 2018 Apr OBJECTIVES: Semaphorin-3A (SEMA3A) and its receptors are found on some immune cells and act as suppressors of immune cells over-activation. Considering the role of SEMA3A and its down-regulation in some autoimmune diseases, as well as our bioinformatics predictions, we assumed that miR-145-5p might affect SEMA3A expression. So, we aimed to determine the effect of miR-145-5p on SEMA3A gene expression level. MATERIALS AND METHODS: In this experimental study, we evaluated the effect of miR-145-5p transfection on SEMA3A expression in peripheral blood mononuclear cells (PBMCs) using ELISA and quantitative real-time polymerase chain reaction (PCR) methods. RESULTS: Our results showed that miR-145-5p is able to decrease SEMA3A expression at both protein and mRNA levels. These data confirmed our previous bioinformatic prediction about the inhibitory effect of miR-145-5p on SEMA3A expression. CONCLUSIONS: These results enlightened us about an unknown aspect of SEMA3A role in some autoimmune disorders like multiple sclerosis (MS) and rheumatoid arthritis (RA) and also proposed SEMA3A as a potential therapeutic approach.
29136797 Unparalleled sample treatment throughput for proteomics workflows relying on ultrasonic en 2018 Feb 1 We report on the new microplate horn ultrasonic device as a powerful tool to speed proteomics workflows with unparalleled throughput. 96 complex proteomes were digested at the same time in 4min. Variables such as ultrasonication time, ultrasonication amplitude, and protein to enzyme ratio were optimized. The "classic" method relying on overnight protein digestion (12h) and the sonoreactor-based method were also employed for comparative purposes. We found the protein digestion efficiency homogeneously distributed in the entire microplate horn surface using the following conditions: 4min sonication time and 25% amplitude. Using this approach, patients with lymphoma and myeloma were classified using principal component analysis and a 2D gel-mass spectrometry based approach. Furthermore, we demonstrate the excellent performance by using MALDI-mass spectrometry based profiling as a fast way to classify patients with rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis. Finally, the speed and simplicity of this method were demonstrated by clustering 90 patients with knee osteoarthritis disease (30), with a prosthesis (30, control group) and healthy individuals (30) with no history of joint disease. Overall, the new approach allows profiling a disease in just one week while allows to match the minimalism rules as outlined by Halls.
29046676 Therapeutic Antibodies: What Have We Learnt from Targeting CD20 and Where Are We Going? 2017 Therapeutic monoclonal antibodies (mAbs) have become one of the fastest growing classes of drugs in recent years and are approved for the treatment of a wide range of indications, from cancer to autoimmune disease. Perhaps the best studied target is the pan B-cell marker CD20. Indeed, the first mAb to receive approval by the Food and Drug Administration for use in cancer treatment was the CD20-targeting mAb rituximab (Rituxan(®)). Since its approval for relapsed/refractory non-Hodgkin's lymphoma in 1997, rituximab has been licensed for use in the treatment of numerous other B-cell malignancies, as well as autoimmune conditions, including rheumatoid arthritis. Despite having a significant impact on the treatment of these patients, the exact mechanisms of action of rituximab remain incompletely understood. Nevertheless, numerous second- and third-generation anti-CD20 mAbs have since been developed using various strategies to enhance specific effector functions thought to be key for efficacy. A plethora of knowledge has been gained during the development and testing of these mAbs, and this knowledge can now be applied to the design of novel mAbs directed to targets beyond CD20. As we enter the "post-rituximab" era, this review will focus on the lessons learned thus far through investigation of anti-CD20 mAb. Also discussed are current and future developments relating to enhanced effector function, such as the ability to form multimers on the target cell surface. These strategies have potential applications not only in oncology but also in the improved treatment of autoimmune disorders and infectious diseases. Finally, potential approaches to overcoming mechanisms of resistance to anti-CD20 therapy are discussed, chiefly involving the combination of anti-CD20 mAbs with various other agents to resensitize patients to treatment.
29040566 Overlapping network meta-analyses on the same topic: survey of published studies. 2017 Dec 1 BACKGROUND: To assess how common it is for a published network meta-analysis (NMA) to have other published overlapping NMAs, and to evaluate these overlaps. METHODS: A total of 88 NMAs of randomized controlled trials evaluating the comparative effectiveness of health interventions were randomly selected. For each of these, we searched for NMAs on the same topic. A random sample of 40 pairs (an index NMA and one of its overlapping NMAs) was selected to assess the overlap in terms of nodes, treatments and references. The topic with the largest number of overlapping NMAs was described in depth. RESULTS: In all, 68 of the 88 index NMAs had at least one overlapping NMA: 77% [95% confidence interval (CI), 69-86%]. We identified 515 pairs of overlapping NMAs. Among the 40 randomly selected pairs, 73% (95% CI, 58-88%) of nodes, 79% (95% CI, 72-86%) of treatments and 48% (95% CI, 37-59%) of references included in the index NMAs were also found in the respective overlapping NMAs. Efficacy of biologics in rheumatoid arthritis had the largest number of overlapping NMAs, with 28 NMAs published between 2003 and 2014. Differences in selection and definition of nodes of treatments resulted in different network geometries. There were also differences in both the direction and the statistical significance of effects. CONCLUSIONS: Published NMAs exhibit extensive overlap and potential redundancy. Erratic retrieval of eligible trials, and lack of consensus on the range of interventions to be considered and how they might be merged or split in different nodes, may cause confusion.
28994016 Cardiopulmonary Manifestations of Collagen Vascular Diseases. 2017 Oct 9 PURPOSE OF REVIEW: The study aimed to illustrate the cardiopulmonary findings of the following collagen vascular diseases on cross-sectional imaging: rheumatoid arthritis, scleroderma (progressive systemic sclerosis), systemic lupus erythematosus, the inflammatory myopathies (polymyositis/dermatomyositis), and Sjögren's syndrome. RECENT FINDINGS: Although collagen vascular diseases can affect any part of the body, interstitial lung disease and pulmonary hypertension are the two most important cardiopulmonary complications and are responsible for the majority of morbidity and mortality in this patient population. Interstitial pneumonia with autoimmune features (IPAF) is a newly described entity that encompasses interstitial lung disease in patients with clinical, serologic, or morphologic features suggestive of but not diagnostic of collagen vascular disease; these patients are thought to have better outcomes than idiopathic interstitial pneumonias. Interstitial lung disease and pulmonary hypertension determine the prognosis in collagen vascular disease patients. IPAF is a new term to label patients with possible collagen vascular disease-related interstitial lung disease. Collagen vascular disease patients are at increased risk for various malignancies.
28969447 Beneficial effects of a probiotic blend on gastrointestinal side effects induced by leflun 2017 Oct 13 Patients with metabolic disorders frequently suffer from side effects induced by long-term oral medications. The present study using a rat model system indicated that leflunomide (LF) and amlodipine (AMD), the active ingredients contained in the medications for rheumatoid arthritis and hypertension, respectively, appeared to induce various bowel problems including constipation and inflammation. In the small and large intestine, LF increased the expression of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 compared to the null control and AMD increased the expression of both TNF-α and IL-1β, although its effect on IL-6 was only increased in the large intestine. It is noteworthy that the probiotic blend tested was found to alleviate intestinal complications caused by LF and AMD. Analysis of the gut microbiota revealed that AMD induced compositional changes in the gut microbiota. Namely, members of the phylum Bacteroidetes, which constituted only about 0.3% of the microbiota in the null control, made up more than 10% of the total composition in the AMD-administered rats. Interestingly, the probiotic blend was also found to normaliSe the gut microbiota.
28938865 Binding of ibuprofen to human hemoglobin: elucidation of their molecular recognition by sp 2018 Sep Ibuprofen, used for the treatment of acute and chronic pain, osteoarthritis, rheumatoid arthritis, and related conditions has ample affinity to globular proteins. Here we have explored this fundamental study pertaining to the interaction of ibuprofen with human hemoglobin (HHb), using multispectroscopic, calorimetric, and molecular modeling techniques to gain insights into molecular aspects of binding mechanism. Ibuprofen-induced graded decrease in absorption spectra indicates protein disruption along with sedimentation of HHb particle. Red shifting of absorption peak at 195 nm indicates alteration in the secondary structure of HHb upon interaction with ibuprofen. Flouremetric and isothermal titration calorimetric (ITC) studies suggested one binding site in HHb for ibuprofen at 298.15 K. However, with increase in temperature, ITC revealed increasing number of binding sites. The negative values of Gibbs energy change (ΔG(0)) and enthalpy change (ΔH(0)) along with positive value of entropy change (ΔS(0)) strongly suggest that it is entropy-driven spontaneous exothermic reaction. Moreover, hydrophobic interaction, hydrogen bonding, and π-π interaction play major role in this binding process as evidenced from ANS (8-anilino-1-napthalenesulphonic acid), sucrose binding, and molecular modeling studies. The interaction impacts on structural integrity and functional aspects of HHb as confirmed by CD spectroscopy, increased free iron release, increased rate of co-oxidation and decreased rate of esterase activity. These findings suggest us to conclude that ibuprofen upon interaction perturbs both structural and functional aspects of HHb.
28874419 Early intervention in Crohn's disease: towards disease modification trials. 2017 Dec Crohn's disease (CD) is a chronic progressive destructive inflammatory bowel disease. As in rheumatoid arthritis, there is increasing evidence that early treatment initiation with disease-modifying agents, such as biological drugs, may lead to complete disease control, prevention of disease progression thus protecting against irreversible damage and restoration of normal quality of life. Data from randomised clinical trials with immunosuppressants and biologics suggest that treating patients with a disease duration of <2 years and an absence of complications may significantly reduce the risk for complications and increase time in remission in patients with CD. Moreover, rapid disease control may effectively prevent disease progression and allow dose reduction or even withdrawal of treatment, reducing the risk of long-term adverse events and healthcare costs. However, prospective disease modification trials are needed to confirm these initial results. Here we review the literature regarding early intervention in adult patients with CD and propose criteria for future disease modification trials.
28872680 Current and novel anti-inflammatory drug targets for inhibition of cytokines and leucocyte 2018 Jan OBJECTIVES: Many studies of disease state mechanisms reveal that unbridled inflammation is to blame for many of the symptoms associated with autoimmune diseases such as Crohn's and Rheumatoid Arthritis (RA). While therapies aimed at decreasing levels of pro-inflammatory cytokines exist, some have failed clinically or have extensive adverse effects. The aim of this review is to discuss common drug targets for anti-inflammatory therapies as well as explore potential mechanisms of action for new therapies. Various studies done on novel mechanisms targeting pro-inflammatory cytokine release as well as leukocyte chemotaxis have been researched for discussion here. Both of these contribute to tissue injury and patient symptoms in inflammatory and autoimmune disease states. KEY FINDINGS: While many current drug targets suppress inflammation via the receptor, research aimed at identifying new compounds and signaling mechanisms is ongoing to identify new targets within pro-inflammatory signaling pathways, or specific immune cell types. CONCLUSIONS: While glucocorticoids and monoclonal antibodies have shown to be efficacious, some patients have encountered mixed results. Biologic therapies also come with a high price tag Thus, novel compounds with new immune drug targets are ideal for patients whose therapies have not been successful.
28854762 Efficacy of Open Debridement and Polyethylene Exchange in Strictly Selected Patients with 2017 Sep 1 PURPOSE: To assess the efficacy of open debridement and polyethylene exchange (ODPE) combined with proper antibiotic therapy in strictly selected patients with infection after total knee arthroplasty (TKA) and analyze factors associated with treatment failure. MATERIALS AND METHODS: From January 2010 to January 2014, 25 cases that underwent ODPE under the diagnosis of infection within four weeks after TKA or acute hematogenous infection within five days of symptom onset were reviewed in this study. RESULTS: Treatment was successful in 22 out of 25 cases (88.0%). Factors associated with failure were accompanying infection (periprosthetic infection in the ipsilateral foot, cervical parotid abscess, and masticator space abscess) and diagnosis of rheumatoid arthritis (RA) before TKA. Resistant bacteria did not entail a risk. On clinical results, the mean postoperative Lysholm score and Korean Knee score were 81.4 and 79.4, respectively, the knee range of motion was 115.4°±12.9°, and duration of hospitalization was 32.3±8.4 days. On radiographic results, 3.47±1.56 mm joint line elevation and a valgus change of 0.61°±2.35° in knee alignment were observed. CONCLUSIONS: ODPE combined with appropriate antibiotics therapy could be a useful treatment method for infection after TKA if the procedure is performed within a symptom duration of five days or less in the absence of accompanying infection in patients whose indication for TKA was not RA.
28819596 Complex Regional Pain Syndrome following an Episode of Herpes Zoster: A Case Report. 2017 Mar INTRODUCTION: Complex regional pain syndrome (CRPS) is characterized by searing pain, hyperalgesia, edema, allodynia, and skin changes. CRPS may be difficult to diagnose and to treat given poorly understood mechanisms as well as its presentation of symptoms that may mimic common conditions such as joint stiffness in this condition as well as rheumatoid arthritis. CASE REPORT: A 71-year-old female presented to our clinic post shingles of the right upper extremity. We diagnosed her with CRPS based on the Budapest diagnostic criteria and the clinical findings of pain and decreased the range of motion along with edema, hypersensitivity, discoloration and allodynia of the right thumb and index finger. She was treated with vitamin C as well as gabapentin and physical therapy. The patient was unable to go consistently to physical therapy due to insurance limitations, and we found no clinical benefit of vitamin C in reducing her symptoms. She was lost to follow-up during her treatment but re-emerged at 21 months. At that time she reported, she was largely unchanged in regards to her right-hand symptoms but did believe the gabapentin was helpful and still continued to take 300 mg daily. CONCLUSION: This case report highlights the usefulness of the Budapest diagnostic criteria to make the diagnosis of CRPS when associated with shingles, which can cause long-term pain and mimic some findings. Prompt diagnosis is important, as recovery typically extends beyond 6 months; our patient still reported continued symptoms at 21 months post initial presentation. Our primary treatment plan was physical therapy, which she discontinued due to insurance limitations. We recommend that patients, physicians, and third-party payers work together to extend access to physical therapy. More investigation is warranted regarding symptomatic treatment, as we found limited clinical benefit of gabapentin and vitamin C.
28724596 Severe destructive nasopharyngeal granulomatosis with polyangiitis with superimposed skull 2017 Jul 19 Skull base osteomyelitis in the setting of granulomatosis with polyangiitis (GPA) is rare and entails significant diagnostic challenges. We present a case of a 65-year-old Caucasian man with a history of rheumatoid arthritis, off immunosuppression for 18 months, who presented with 2 years of chronic headaches, severe fatigue, saddle nose deformity and 20-kilogram unintentional weight loss. Maxillofacial CT revealed an extensive destructive sinonasal and erosive skull base process. Laboratory evaluation showed equivocal elevation of antiproteinase 3 antibodies with negative antineutrophil cytoplasmic antibody panel. Biopsy of the skull base/clivus revealed necrotising granulomatous inflammation with focal vasculitis consistent with GPA, and multiple bone cultures were positive for Pseudomonas aeruginosa This patient was diagnosed concurrently with GPA and P. aeruginosa skull base osteomyelitis. He was started on a 6-week course of cefepime intravenously and oral prednisone, with the plan to initiate rituximab infusion 2 weeks after initiation of antibiotic therapy.
28364136 Relapsing polychondritis: a chameleon among orphan diseases. 2017 Jun Relapsing polychondritis (RPC) is a rare disease with recurrent episodes of inflammation of cartilage tissue leading to fibrosis and organ damage. Despite unknown etiology, there is some evidence of a genetic predisposition. The clinical presentation is heterogeneous and an association with other autoimmune disorders such as rheumatoid arthritis or different forms of vasculitis has been described. All organ systems containing cartilage can be affected, such as ear, nose, joints, trachea, aorta, and coronary arteries. Given the broad spectrum of potential manifestations, a variety of medical specialists may be involved in the management of RPC patients. As establishing the diagnosis of RPC may be difficult, an interdisciplinary approach may be preferable. Treatment options include glucocorticoids, dapsone, disease-modifying antirheumatic drugs, and biologics. Prognosis is as heterogeneous as the clinical picture, depending on the severity of organ damage. In this paper we give an overview of the current knowledge with regard to pathogenesis, clinical picture, diagnosis, and therapy of RPC.
27859213 Role of Wnt5a in the Pathogenesis of Inflammatory Diseases. 2017 Jul Wnt5a initiates pro-inflammatory responses through activation of non-canonical Wnt signaling pathway. Pro-inflammatory functions of Wnt5a trigger pro-inflammatory signaling cascades and increase secretion of pro-inflammatory cytokines and chemokines. Wnt5a as a potent signaling molecule is strongly implicated in a number of diseases including cancer, diabetes, metabolic disorders, and of special interest in this review, inflammatory diseases. This review summarizes the role of Wnt5a in the pathogenesis of inflammatory diseases including atherosclerosis, rheumatoid arthritis, psoriasis vulgaris and sepsis, promoting greater understanding, and clinical management of these diseases. J. Cell. Physiol. 232: 1611-1616, 2017. © 2016 Wiley Periodicals, Inc.
27826114 Nocardia elegans infection: a case report and literature review. 2017 Jan A case of disseminated nocardiosis caused by Nocardia elegans in a 72-year-old man with rheumatoid arthritis, treated with tacrolimus and prednisolone, is reported herein. The patient had impaired vision and was diagnosed with endophthalmitis and an abdominal skin abscess. He was started on trimethoprim-sulfamethoxazole treatment, followed by cefepime. The patient was then switched to a combination of imipenem-cilastatin and minocycline. Although the patient survived as a result of surgery and prolonged antibiotic treatment, he eventually lost vision after the infection became resistant to antibiotic treatment. Molecular analysis of samples from the abscess and vitreous fluid confirmed the extremely rare pathogen N. elegans, which accounts for only 0.3-0.6% of infections caused by Nocardia species. This organism is almost always associated with pulmonary infection, and disseminated infections are rare. As with previously reported norcardial infections, the current case was treated successfully with trimethoprim-sulfamethoxazole, carbapenems, and aminoglycosides. However, the clinical characteristics of this organism remain unclear. Further studies are therefore required to develop more effective treatment protocols for disseminated nocardiosis caused by this problematic pathogen.
28550835 [Severe Interstitial Lung Disease and Manic Symptoms Secondary to Corticosteroids in a Pat 2017 Mar 31 Interstitial lung disease occurs in up to 25% of patients with Sjögren's syndrome and 2% - 8 % of patients with systemic lupus erythematosus. Corticosteroid therapy remains the main treatment for systemic lupus erythematosus. However, it can be associated with several neuropsychiatric disorders especially with prednisolone at a dose of more than 40 mg/day. We present the case of a 51-year-old patient with systemic lupus erythematosus and secondary Sjögren's syndrome with severe pulmonary involvement four years after the diagnosis. Chest computed tomography revealed neofibrosis and ground glass appearance pattern. After increasing the dose of prednisolone to 60 mg/day, the patient presented a manic episode. There was need of hospitalization and the situation was considered to be secondary to corticosteroids at high doses. Central neurological involvement by organic disease was excluded. We introduced monthly perfusion of cyclophosphamide for six months and later started mycophenolate mofetil 2 g/day, reducing prednisolone to 10 mg/day and maintaining hydroxychloroquine 400 mg/day, with control of disease activity.
27798360 Objectively measured physical activity and its influence on physical capacity and clinical 2017 Jun Objective The objectives of this paper are to objectively measure habitual physical activity levels in patients with primary Sjögren's syndrome (pSS) with mild disease activity and to determine to which extent it may be associated with physical capacity and function and clinical features. Methods In this cross-sectional study, 29 women with pSS were objectively assessed for habitual physical activity levels (using accelerometry) and compared with 20 healthy women (CTRL) frequency-matched for physical activity levels, age, body mass index, and body fat percentage with regard to physical capacity and function, fatigue, depression, pain, and health-related quality of life. Results pSS showed 8.5 min/day of moderate-to-vigorous physical activity (MVPA) when only MVPA accumulated in bouts ≥ 10 min was considered; when considering total MVPA (including bouts < 10 min), average levels were 26.3 min/day, with 62% of pSS patients achieving the recommendation (≥ 21.4 min/day). Moreover, pSS showed lower VO(2peak), lower muscle strength and function, higher fatigue, and poorer health-related quality of life when compared with CTRL ( p < 0.05). These differences (except for aerobic capacity) were sustained even when only individuals achieving the minimum of 21.4 min/day of total MVPA in both groups were compared. Finally, MVPA time was significantly correlated with aerobic conditioning, whereas total counts and sedentary time were associated with lower-body muscle strength and the bodily-pain domain of SF-36 in patients with pSS. Conclusion When compared to physical activity-matched healthy controls, pSS patients showed reduced physical capacity and function, increased fatigue and pain, and reduced health-related quality of life. Except for aerobic conditioning, these differences were sustained when only more physically active participants were compared, indicating that minimum recommended levels of physical activity for the general population may not be sufficient to counteract pSS comorbidities.
28573480 Relationship of miRNA-146a to primary Sjögren's syndrome and to systemic lupus erythemato 2017 Aug Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE) are common systemic autoimmune diseases, which impact not only patient health but also their quality of life. miRNA-146a is a microRNA that participates in the pathophysiology of SjS and SLE. In this investigation, we conducted a meta-analysis to determine the relationship of miR-146a to primary SjS (PSS) and to SLE. The following databases were interrogated; Pubmed, Cochrane Central Register of Controlled Trials, WANFANG, Chinese National Knowledge Infrastructure, and WEIPU. Standard mean difference with 95% confidence intervals (CI) were used to study the relationship between miRNA-146a expression and thee diseases by random-effects model. A total of six studies, with 158 cases and 124 controls were included for the meta-analysis. The meta-analysis shows that miRNA-146a expression is associated with the risk of PSS (MD = 6.32, p = 0.005). No relationship between miR-146a expression and SLE was identified (MD = -0.86, p = 0.26). SLE subgroup analysis (peripheral blood mononuclear cells and serum) confirmed this result. The risk for PSS is related to miR-146a expression, while miRNA-146a expression is not related to SLE. As such, miRNA-146a may serve as a novel biomarker for the diagnosis of PSS, but not SLE.
28361884 AT-RvD1 Promotes Resolution of Inflammation in NOD/ShiLtJ mice. 2017 Mar 31 Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease characterized by diminished secretory function of the exocrine glands. Treatments for hyposalivation are limited to the use of saliva substitutes and medications that provide only temporary relief. In light of the high degree of need and the limitations of current therapies, development of alternative treatments to restore functioning is essential. Resolvins (Rv), which are highly potent lipid mediators, offer a viable alternative for better treating inflammatory diseases such as SS. The goal of this study was to determine whether systemic preventive treatment with Aspirin-triggered RvD1 (AT-RvD1) reduces inflammation and preserves secretory functioning in NOD/ShiLtJ SS-like mice. Our results indicate that systemic treatment with AT-RvD1 diminishes the progression of the disease in salivary epithelium from female mice as follows: (a) improves secretory function, (b) reduces pro-inflammatory molecule gene expression, (c) increases anti-inflammatory molecule gene expression and (d) induces M2 macrophage polarization. Finally, AT-RvD1 decreases lymphocytic infiltration into the salivary glands when used with small doses of the steroid, dexamethasone, and promotes the tissue healing process.
28124217 Elemental Analysis of Whole and Protein Separated Blood Serum of Patients with Systemic Lu 2017 Sep Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are systemic autoimmune diseases with complex symptoms and pathogenesis that are still not completely understood. Several studies showed that the trace element homeostasis and also the levels of antioxidant plasma proteins are changed in autoimmune disorders; however, these results are controversial. In this study, the potassium (K), calcium (Ca), magnesium (Mg), copper (Cu), zinc (Zn), and iron (Fe) concentrations of the serum and proteins-immunoglobulin G (IgG), transferrin (Trf), albumin (Alb), and ceruloplasmin (Cp)-separated from serum samples by affinity chromatography were determined in patients with SLE and SS. Ca and K levels were found to be decreased in the case of both disorders compared to the control group, and the competitive antagonism of Cu and Zn was also observed: elevated Cu concentration together with a lower Zn concentration was measured in the sera of patients with autoimmune diseases. After fractionation, the trace element concentration of protein containing fractions altered to that of the control group. In case of the autoimmune disorders, the highest Cu concentration was determined in the Alb-containing protein fractions while the Zn level decreased in the Alb and increased in the Cp as well as in the IgG- and Trf-containing fractions compared to the healthy samples. Changes have also been found in the level and distribution of K and Ca.