The problem of residual pain in the assessment of rheumatoid arthritis activity.

Residual pain is a major unmet medical need observed in patients suffering from rheumatoid arthritis (RA), which decreases their quality of life, even after achieving remission or low disease activity. The article has two aims: 1) to present mechanisms involved in the pathophysiology of residual pain, both inflammatory and non-inflammatory, i.e. neuropathic and nociplastic pain, as well as secondary pain syndromes, i.e. osteoarthritis and fibromyalgia, which can contribute to residual pain; 2) to show the limitations of current disease activity measures recommended by European Alliance of Associations for Rheumatology (EULAR) and American College of Rheumatology (ACR), which raise the need for a separate assessment of pain, and examples of methods that could be used by medical professionals to assess the pain and make a differential diagnosis. In conclusion, establishing a valid method to assess pain is essential to identify the pathomechanism of residual pain and to create treatments tailored specifically to individual RA patients.

Liquid Biopsy and Its Emerging Role in Rheumatology.

Liquid biopsy is a rapidly evolving diagnostic technique used to analyze tissue-derived information found in the blood or other bodily fluids. It represents a new way to guide therapeutic decisions, mainly in cancer, but its application in other fields of medicine is still growing. Here, we discuss how liquid biopsy has been used in autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, or primary Sjögren's syndrome. Additionally, in aspect of liquid biopsy, we analyze the molecular biomarkers utilized in the field of rheumatology, including circulating cell-free DNA, microRNA, and proteomic content.

Dysbiosis, gut-blood barrier rupture and autoimmune response in rheumatoid arthritis and schizophrenia.

The primary cause of chronic autoimmune diseases is elusive both in somatic medicine and psychiatry. Examples of such conditions are rheumatoid arthritis and schizophrenic disorders. Immune disturbances occur in both diseases, but it is difficult to combine them into a meaningful pathogenetic model. The immunological hypothesis of schizophrenia is based on non-specific changes in the cytokine system and exponents of chronic inflammation in some patients. In rheumatoid arthritis the cytokine network is much better known than in schizophrenia, and interleukin-6, tumor necrosis factor or Janus kinases became a target of treatment. Microbiome dysbiosis and disturbances of the blood-gut barrier may be a new hypothesis of the pathogenesis of somatic and psychiatric diseases. The purpose of this narrative review was to show, using the example of two chronic diseases - rheumatoid arthritis and schizophrenic disorders - that disturbances in the blood barrier of the intestine can be a common mechanism of somatic and mental disorders. The paper presents the current state of knowledge on the hypothetical relationship between microbiome dysbiosis and the pathogenesis of schizophrenia and rheumatoid arthritis. In conclusion, in the light of discoveries regarding the microbiome-gut-brain axis the immunological model of rheumatoid arthritis and schizophrenia formation may gain importance and contribute to the creation of new strategies for causal treatment of these still incurable diseases.

Copper, Iron, and Manganese Toxicity in Neuropsychiatric Conditions.

Copper, manganese, and iron are vital elements required for the appropriate development and the general preservation of good health. Additionally, these essential metals play key roles in ensuring proper brain development and function. They also play vital roles in the central nervous system as significant cofactors for several enzymes, including the antioxidant enzyme superoxide dismutase (SOD) and other enzymes that take part in the creation and breakdown of neurotransmitters in the brain. An imbalance in the levels of these metals weakens the structural, regulatory, and catalytic roles of different enzymes, proteins, receptors, and transporters and is known to provoke the development of various neurological conditions through different mechanisms, such as via induction of oxidative stress, increased α-synuclein aggregation and fibril formation, and stimulation of microglial cells, thus resulting in inflammation and reduced production of metalloproteins. In the present review, the authors focus on neurological disorders with psychiatric signs associated with copper, iron, and manganese excess and the diagnosis and potential treatment of such disorders. In our review, we described diseases related to these metals, such as aceruloplasminaemia, neuroferritinopathy, pantothenate kinase-associated neurodegeneration (PKAN) and other very rare classical NBIA forms, manganism, attention-deficit/hyperactivity disorder (ADHD), ephedrone encephalopathy, HMNDYT1-SLC30A10 deficiency (HMNDYT1), HMNDYT2-SLC39A14 deficiency, CDG2N-SLC39A8 deficiency, hepatic encephalopathy, prion disease and "prion-like disease", amyotrophic lateral sclerosis, Huntington's disease, Friedreich's ataxia, and depression.

Antimitochondrial Antibodies and Primary Biliary Cholangitis in Patients with Polymyalgia Rheumatica/Giant Cell Arteritis.

Background and Objectives: Laboratory liver abnormalities can be observed in patients affected with polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA), especially with a cholestatic pattern. The first objective of our review article is to discuss the potential link between antimitochondrial antibodies (AMA) and/or primary biliary cholangitis (PBC) and PMR/GCA, according to the evidences of literature. The second objective is to discuss the association of PMR/GCA with the other rheumatic diseases having PBC as a common manifestation. Materials and Methods: A literature search was performed on PubMed and Medline (OVID interface) using these terms: polymyalgia rheumatica, giant cell arteritis, antimitochondrial antibodies, primary biliary cholangitis, primary Sjogren's syndrome, systemic sclerosis, and systemic lupus erythematosus. The search was restricted to all studies and case reports published in any language. Reviews, conference abstracts, comments, and non-original articles were excluded; however, each review's reference list was scanned for additional publications meeting this study's aim. When papers reported data partially presented in previous articles, we referred to the most recent published data. Results and Conclusions: Our literature search highlighted that cases reporting an association between AMA, PBC and PMR/GCA were very uncommon; AMA antigenic specificity had never been detected and biopsy-proven PBC was reported only in one patient with PMR/GCA. Finally, the association of PMR/GCA with autoimmune rheumatic diseases in which PBC is relatively common was anecdotal.

IgA immunoglobulin isotype of rheumatoid factor in primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is an autoimmune disease with autoantibodies overproduction, including rheumatoid factors (RF). RF-IgA, IgG immunoglobulin classes are suggested as potential biomarkers of pSS. We studied 76 patients with pSS (ACR/Eular 2017); laboratory tests included ESR, C-reactive protein, concentrations of gamma globulins, RF, Anti-SS-A/Ro, and anti-SS-B/La. Eye dryness and keratoconjunctivitis sicca were confirmed with Schirmer's test, the ocular staining score (OSS) using lissamine green, fluorescein staining and biopsy of minor salivary gland with the histopathological evaluation. Differences between groups were analyzed with U Mann-Whitney test. Correlations between quantitative variables were assessed with the Spearman correlation coefficient.. The best diagnostic values of immunoglobulin concentration for discriminating pSS patients and healthy individuals are for RF-IgA. With cut-off of 21.5 EU/mL, the sensitivity is 72% and specificity is 100%. Very high specificity (100%) is also obtained for RF-IgM concentration of 74.1 EU/mL. Sensitivity is, however, smaller than that for RF-IgA and amounted to 61%. The RF-IgG is the poorest indicator of pSS with 51% of sensitivity and 95% of specificity. To summarize RF-IgA strongly associate with anti-SS-A and anti-SS-B autoantibodies. Both RF-IgA and RF-IgM may be used as diagnostic tools for pSS. Conclusions: among the three studied rheumatoid factor subtypes, RF-IgA showed the best diagnostic accuracy for pSS. RF-IgA correlated with anti-SS-A/Ro and anti-SS-B antibodies even more closely than RF-IgM. The assessment of the RF-IgA serum concentration may be helpful in the process of establishing pSS diagnosis.

High-resolution ultrasound imaging of skin involvement in systemic sclerosis: a systematic review.

To collect evidence on the application of ultrasound in skin assessment in patients with systemic sclerosis (SSc). The authors carried out a review of the literature via Pubmed MEDLINE database. The search terms were: skin imaging in systemic sclerosis, ultrasound skin imaging in patients with systemic sclerosis. The selection and analysis of articles were performed by two independent evaluators. The authors analyzed 10 studies characterizing 470 patients with systemic sclerosis. The patients were young adults, mainly women. The described methods of ultrasound were: ultrasound elastography (7.14%), ultra-high-frequency (7.14%) and B-mode ultrasonographic imaging (21.43%), high-frequency ultrasonography (21.43%), shear-wave elastography (21.43%) and others (21.43%). Skin measurements reported in the analyzed studies were: skin ultrasound in all studies, skin thickness (8 studies), skin elasticity (5 studies), skin stiffness (2 studies), subcutaneous tissue thickness (1 study). Ultrasound measurements were compared to different types of scales and measurements used in the description of disease progression. Ultrasound may be used in the clinical assessment of skin involvement in SSc. To the best of our knowledge, articles currently reporting the use of ultrasound in skin imaging show interesting ideas and provide basis for further research. Skin involvement in SSc assessed with ultrasound should be compared to skin biopsy. It is necessary to develop guidance for conducting skin measurements using ultrasound in patients with scleroderma. Currently, skin imaging in SSc is of limited clinical use due to a variety of methods and the lack of a standard operating procedure. The authors of analyzed studies suggested that high-frequency ultrasound provided a quantitative and reliable evaluation of dermal thickness in patients with SSc.

The Role of IgG4 in Autoimmunity and Rheumatic Diseases.

The distinguishing of the IgG4-related disease (IgG4-RD) from among other rheumatic diseases has brought attention to the IgG4 subclass of immunoglobulins. It is the least numerous subclass among immunoglobulins G. In general, IgG4 is considered to be non-inflammatory and tolerance inducing, due to its unique structure. However, in IgG4-RD this antibody plays a pathogenic role in activation of the fibrinogenesis and of the inflammatory process; there are also suggestions that it may be a marker of an abnormal inflammatory response. The importance of IgG4 for the pathogenesis of allergic diseases, with a vital role of its ratio to immunoglobulin E (IgE/IgG4 ratio), has been known for years. The role of IgG4 in the course and pathogenesis of rheumatic diseases is still being researched and is not yet fully understood. Increased IgG4 levels have been revealed in rheumatoid arthritis, although no clear link between this phenomenon and disease activity has been demonstrated. There are articles on the potential importance of IgG4 concentration (of both elevated and decreased serum levels) in Sjogren's syndrome. Additionally, anti-nuclear IgG4 antibody significant titers have been detected in SLE patients, and it has been suggested that the effect of these antibodies on complement consumption and the production of proinflammatory cytokines may play a role in inhibiting the progression of SLE. IgG4 plays a role in autoimmune diseases other than rheumatic diseases, such as pemphigus, bullous pemphigoid, idiopathic membranous glomerulonephritis, or myasthenia gravis, but also in helmints infections. Research shows the importance of IgG4 in malignancy of neoplasms. Melanoma cells are known to stimulate IgG4 production through a modified Th2-based inflammatory response. The role of this immunoglobulin in cholangiocarcinoma is also considered as possible. The aim of this review article is to discuss the current knowledge of IgG4 not only from the perspective of the IgG4-RD but also from a point of view of other autoimmune diseases with particular emphasis on rheumatic diseases.

Autoimmune syndrome induced by adjuvants after breast enhancement with polyacrylamide hydrogel: a study in Poland.

Autoimmune syndrome induced by adjuvants (ASIA) is the spectrum of diseases in which the substances considered inert to the body induce autoimmune reactions and inflammation. Some of the biomaterials recently used in plastic surgery, such as silicone or polyacrylamide hydrogel (PAAG) seem to trigger clinical features of ASIA. The aim of this study was to assess the incidence of these features within a group of women after breast augmentation with PAAG. As many as 30 consecutive patients (26-59 years, mean age 39.5) referred to the Clinic of Plastic Surgery after breast enhancement with PAAG were examined. The validated criteria of ASIA syndrome were employed. Descriptive statistics were chosen based on the distribution of variables. The research was approved by the Bioethical Committee of the Centre of Postgraduate Medical Education in Warsaw, Poland. Within the studied group, 50% of patients (n = 15) fulfilled ASIA diagnostic criteria. Apart from local complications, we encountered various general symptoms, among which fever (n = 13, 43.3%), tingling and numbness of upper extremities (n = 10, 33.3%) and chronic fatigue (n = 9, 30%) were the most common. These symptoms were present on an ambulatory visit, before qualification to the operation of hydrogel removal. All patients undergoing surgical PAAG removal (n = 8) declared alleviation or complete resolution of the symptoms. Polyacrylamide hydrogel breast filling, although limiting the invasiveness of the procedure in relation to silicone breast implants, also carries the risk of developing ASIA symptoms. The removal of PAAG may bring improvement in some cases.

The role of Epstein-Barr virus infection in primary Sjögren's syndrome.

PURPOSE OF REVIEW: The purpose of this article is to draw attention to the role of Epstein-Barr virus (EBV) virus in the pathogenesis of the primary Sjögren's syndrome. The article introduces the problem of consequences of EBV acute infection, and its reactivation, in association with the immune response modulation by the virus and with an increased risk of developing systemic autoimmune diseases and EBV-associated cancers. RECENT FINDINGS: The knowledge about the mechanisms by which the virus may stay for years in a latent phase, unrecognized by the host response immune cells is constantly expanding. There are several mechanisms and theories about EBV influence on the autoimmune process in Sjogren's syndrome (pSS), including the similarity (molecular mimicry) between viral EBNA-2 protein and Ro-60 antigen or EBER-1 and EBER-2 viral proteins and La antigen. SUMMARY: The influence of EBV infection on the development and course of pSS has been proven. It has also been established that both EBV and pSS result in the increased risk of tumor (especially lymphoma) development. In the light of these findings, new ways to manage EBV infections are being sought. Optimal methods for assessing EBV infection status are being devised. Research also aims at finding therapies, which target EBV through the inhibition of the autoimmune process and of viral activity. The present article is an attempt to discuss the most important phenomena and elements linking EBV infection to the primary Sjögren's syndrome.

Usefulness of rheumatoid factor as an immunological and prognostic marker in PSS patients.

INTRODUCTION: The rheumatoid factor (RF) is present in numerous autoimmune disorders, although its role in many of them remains a subject of research. The study assesses the role of RF as an immunological and prognostic factor in the primary Sjögren's syndrome (pSS). METHODS: Seventy-five pSS patients (mean age 50.03 ± 15.1), 65 (87%) females, and 10 (13%) males. WBC, CRP, RF, ESR, gammaglobulins, C4, C3 component of complement, cryoglobulins, ANA, anti-SS-A, and anti-SS-B antibodies were determined. The disease activity assessed with ESSDAI. Minor salivary gland biopsy (focus score and immunochemistry) was conducted. Results were analyzed with U Mann-Whitney (continuous variables) tests, correlations between quantitative variables assessed with the Spearman correlation coefficient with statistical significance set at p < 0.05. The approval of the Bioethics Committee was obtained. RESULTS: Two subgroups I-RF(+) (61%) and II-RF(-) (39%) were established, with lower WBC (p = 0.012) and higher ESR (p = 0.016), gammaglobulin concentration (p = 0.007) in group I. Conjunctivitis sicca was more severe in group I. There was positive correlation between RF and lnANA (rho = 0.496), anti-SS-A, anti-SS-B antibodies (rho = 0.448; rho = 0.397 respectively). There was higher disease activity ESSDAI in group I than in group II (Me, 3.0 vs 2.0; p < 0.003). RF correlated negatively with WBC (rho = - 0.374). RF did not correlate with serum concentrations of BAFF, APRIL, CRP, and C3, C4 and with CD19+, CD3+, CD4+, CD 21+, and CD35+. CONCLUSIONS: RF should be considered as a prognostic, but not diagnostic, factor in patients with pSS, as it is associated with more severe disease course (sicca eye symptoms, ESSDAI) and parameters (production of gammaglobulins, ANA, anti SS-A, anti-SS-B autoantibodies) indicating increased B cell activity.

The level of TGF-ß in sera of patients with primary Sjögren's syndrome.

OBJECTIVES: Tumor growth factor ß (TGF-ß) is a pleiotropic cytokine which controls autoimmune reactions, cell proliferation, and the organ accumulation of lymphocytes. This cytokine has a protective and anti-inflammatory effect in autoimmune processes, but also has a pro-fibrinous activity. Therefore, its importance in the development of systemic sclerosis has been proven. The role of TGF-ß in Sjögren's syndrome is also a valid direction of research. The aim of the presented study is to evaluate the level of TGF-ß in sera of primary Sjögren's syndrome patients and to investigate possible correlations with autoantibodies, cytokines, and cells in biopsy of minor salivary glands active in the pathogenesis of this syndrome. MATERIAL AND METHODS: Thirty-three primary Sjögren's syndrome patients were included. Routine laboratory tests and immunological assessment (ANA, anti SS-A, anti SS-B antibodies, rheumatoid factor), ophthalmological assessment with ocular staining scoring, chest X-ray, and high-resolution computed tomography (if necessary) were performed. Serum concentrations of cytokines such as TGF-ß, BAFF, APRIL, FLT-3L, LT-α, IL-21, and TNF-α were evaluated using standard ELISA assays. The histopathological evaluation (focus score) and the determination of CD3+, CD4+, CD19+, CD21+, CD35+ cells was performed. RESULTS: There was no significant correlation between TGF-ß and other tested cytokines or autoantibodies, other than TNF-α. A negative correlation (ρ = -0.472) between TGF-ß and TNF-α was found. There were no correlations between TGF-ß and: results of ocular examinations, elements of histopathological variables, or lungs changes. CONCLUSIONS: The authors state that: 1) the results may indicate that TGF-ß influences the serum TNF-α activity in pSS patients, 2) our findings suggest that TGF-ß may be the strongest inhibitor of TNF-α among cytokines involved in pSS pathogenesis, and 3) the results may explain the ineffectiveness of anti-TNF drugs in the treatment of pSS.

The prevalence of ANA antibodies, anticentromere antibodies, and anti-cyclic citrullinated peptide antibodies in patients with primary Sjögren's syndrome compared to patients with dryness symptoms without primary Sjögren's syndrome confirmation.

OBJECTIVES: Our study analyses the prevalence of ANA, anti-SS-A, anti-SS-B, and ACA and ACPA antibodies in patients with pSS and with dryness symptoms without pSS confirmation, and the association of ACPA and ACA antibodies with specific clinical symptoms. MATERIALS AND METHODS: 113 patients were divided into two groups: I - with diagnosed pSS (N = 75); and II - with dryness without pSS evidence (N = 38). Diagnostics: indirect immunofluorescence (IF; Hep-2 cell line) of antinuclear antibodies (ANA), anti-SS-A anti-SS-B antibodies determined with semi-quantitative method, autoantibody profile (14 antigens, ANA Profil 3 EUROLINE); basic laboratory, ophthalmic examination tests, minor salivary gland biopsy with focus score (FS), joint and lung evaluation, and ESSDAI questionnaire (pSS activity). RESULTS: 88% of group I had ANA antibodies (1 : 320 titre), 5.3% at 1 : 160. Anti-SS-A antibodies were present in 88% of group I, including all ANA 1 : 160. Anti-SS-A antibodies positively correlated with greater and moderate activity of ESSDAI 5 (p = 0.046) and FS. The presence of SS-B antibodies significantly affected disease activity. ACPA present: group I - 13% (associated with higher arthritis incidence; p = 0.003); group II - 8%. ACA antibodies present in 4% of group I, but not in group II. No ACA association with interstitial lung changes (small ACA + group excludes full conclusions). CONCLUSIONS: ANA antibodies should also be considered in a titre of less than 1 : 320, but the presence of anti-SS-A antibodies is still the most important immunological marker for pSS. Anti-SS-A antibodies correlate with higher disease activity (ESSDAI ≥ 5) and higher FS. The presence of the anti-SS-B antibody was significantly affected by higher activity of the disease. The incidence of arthritis was higher in patients with ACPA+ pSS compared to ACPA- (p = 0.003). There was no relationship between ACPA and arthritis in patients with dry-type syndrome without diagnosis of pSS.

Polymyositis and dermatomyositis as a risk of developing cancer.

Polymyositis (PM) is an idiopathic inflammatory myopathy that affects striated muscles. Dermatomyositis (DM) is an idiopathic inflammatory myopathy with presence of skin symptoms. Both are characterized by acute or subacute onset, symmetrical proximal muscle weakness, the presence of mononuclear cell infiltrates of the muscles and increased activity of muscle enzymes. The treatment still remains glucocorticoids and disease-modifying drugs. Symptoms of PM/DM can be a signal of developing cancer. Known risk factors for cancer in patients with PM/DM are older age, male gender, dysphagia, skin necrosis, cutaneous vasculitis, rapid onset of the disease, elevated creatinine kinase (CK) and C reactive protein (CRP), and an increase in the erythrocyte sedimentation rate (ESR). Recently three new myositis-specific autoantibodies (MSA) predicting the risk of cancer have been discovered: melanoma differentiation-associated protein 5 (anti-MDA-5), transcription intermediary factor 1γ (TIF-1γ), and nuclear matrix protein NXP-2.

Sjögren's syndrome: still not fully understood disease.

Primary Sjögren's syndrome is an autoimmune disorder with external exocrine glands dysfunction and multiorgan involvement. The pathogenesis of primary Sjogren's syndrome is still unclear; however, our knowledge of the involvement of different cells (e.g., B and T cells, macrophages and dendritic cells) and pathways (BAFF/APRIL and interferons) leading to the development of autoimmunity is continually expanding. For clinicians, the most frequent symptoms are dryness of eyes and mouth, but often the patients have musculoskeletal symptoms and systemic manifestations. However, the increased risk of lymphoproliferative disorders in this group of patients, most commonly B-cell marginal zone lymphoma, is particularly important. Recent separation of IgG4-related diseases and attempts to create further diagnostic criteria for pSS testify to the difficulties, and at the same time a large interest, in understanding the disease so as to allow the effective treatment. This article draws attention to the problems faced by the clinician wishing to securely identify pSS by using accurate laboratory biomarkers and useful imaging tools and predict the development of complications associated with this, still not fully understood, autoimmune disease.

The usefulness of ultrasound in the diagnostics of Sjögren's syndrome.

Sjögren's syndrome is an autoimmune exocrinopathy which manifests itself with dryness of the eyes and the oral cavity. These symptoms comprise a so-called sicca syndrome (xerostomia and xerophthalmia). Two forms of this disease may be distinguished: primary Sjögren's syndrome which affects salivary glands and secondary Sjögren's syndrome with other autoimmune diseases present such as rheumatoid arthritis, systemic lupus erythematosus or systemic scleroderma. The diagnosis is based on the classification criteria established in 2002 by a group of American and European scientists (American-European Consensus Group), which involve the interview and physical examination as well as serological, histopathological and radiological tests. Most of these examinations show some limitations such as invasiveness, expensiveness or limited accessibility. The latest research suggests that ultrasound examination may appear promising in the diagnostics of the main salivary glands: submandibular and parotid glands. It is an accessible and relatively cheap examination with high sensitivity and specificity values which are comparable to those obtained via conventional means used in the diagnostics of this disease, i.e. biopsy of the minor salivary glands, sialography and scintigraphy, as well as superior to those obtained in sialometry and Schirmer's test. Additionally, ultrasonography correlates with the results of magnetic resonance imaging. Therefore, a number of authors claim that US examination should be included in the classification criteria of Sjögren's syndrome. The aim of this article is to present the diagnostic capacity of the US examination in Sjögren's syndrome using the current ultrasound classification systems based on the grey-scale, Doppler and contrast-enhanced examinations. The latest research confirms that the most valuable diagnostic criterion in Sjögren's syndrome is the heterogeneity of the glandular parenchyma. The outcome of the examination greatly depends on the examiner's experience.

[Amyloidosis--diagnostic difficulties. A case report of localized amyloidosis]. / Amyloidoza--trudnosci diagnostyczne. Opis przypadku amyloidozy miejscowej.

Amyloidosis consists of a group of clinical disorders caused by extracellular deposition of insoluble protein fibrils which present beta pleated sheets configuration. Such structure makes fibrils resistant to proteolysis. Amyloidosis can be of acquired or hereditary origin. Amyloid deposits can accumulate in locally (localized amyloidosis) or simultaneously in many organs (systemic amyloidosis). Unclear pathogenesis and varied etiology result in particular diagnostic difficulties. Current article attempts to discuss this problem. Presented clinical case of a patient with the amyloid tumor in nosopharynx and positive staining for amyloid in abdominal fat tissue biopsy serves as an example of the diagnostical proceedings in amyloidosis. Congo red staining and red-green birefringence under cross--polarized light of histological specimens still remains a standard procedure in amyloidosis diagnostics. Such methods, however, do not allow to determine the type of the precursor protein, and thus the type of amyloidosis. Thus immunohistochemical tests constitute the next diagnostic phase. Currently, expanded diagnostic capabilities of SAP scintigraphy and of DNA sequencing (establishing transthyretin and apolipoprotein mutations) are also available. Research is carried out on the usefulness of fluorescence spectroscopy in the diagnosis of secondary amyloidosis. Mass spectrometry is used in combination with two-dimensional gel electrophoresis techique for the analysis of protein profiles.