The complement system in primary Sjögren's syndrome: the expression of certain cascade and regulatory proteins in labial salivary glands - observational study.

INTRODUCTION: The complement cascade and regulatory proteins are involved in the pathogenesis of the Sjögren's syndrome and other autoimmune diseases. The complement activation via the alternative pathway was recognized as a major pathogenic mechanism in autoimmune conditions. The aim of this study was to assess expression of complement cascade components and regulatory proteins in minor salivary glands in patients with primary Sjögren's syndrome (pSS). MATERIALS AND METHODS: The expression of C1q and C5b-9 - membrane attack complex and regulatory proteins such as: membrane cofactor protein (MCP), decay-accelerating factor (DAF) and protectin were examined using immunochemistry method in specimens from biopsy of minor salivary glands in pSS patients. The biopsy material was obtained from 20 pSS patients, 5 patients with non-specific sialadenitis and from 5 patients with suspicion of dryness syndrome without sialadenitis confirmation. RESULTS: None of the examined samples showed the expression of C1q or the effector C5b-9. Membrane cofactor protein expression was lower in pSS group than in both non-specific sialadenitis and noninflamed salivary glands. The inflammatory cells in pSS samples partially expressed MCP. There were differences in the sites and intensity of membrane protectin expression exclusively on the luminal surfaces in pSS; on the luminal and, partially, antiluminal surface in non-specific inflammation, and on the entire cell surface in unaffected salivary glands. There were no DAF expression in salivary gland tissue in biopsy specimens in all studied subjects. CONCLUSIONS: The study demonstrated the absence of complement-cascade proteins (C1q, MAC) in the salivary glands of pSS patients, which may indicated a lack of local complement activation via the classical pathway and the observed gland tissue damage being due to a mechanism other than MAC-induced cytolysis. The differences in the expression of complement regulatory proteins between pSS, non-specific sialadenitis, and normal salivary glands may indicate that alternative functions of these regulatory proteins may be of greater significance in pSS. Low MCP expression in pSS in comparison with non-specific sialadenitis and normal salivary glands, may suggest altered modulation of cell-mediated immunity in pSS. The differences in the location and intensity of protectin (CD59) expression indicates a possibility of reducing the proinflammatory effect of protectin in pSS.

IgG4-related disease: why is it so important?

IgG4-related disease (IgG4-RD) is a recently defined systemic inflammatory and fibrous condition of unknown etiology and multiple clinical presentations. Characteristic features include elevated serum IgG4 levels in approximately 70% of patients; diffuse lymphoplasmocytic infiltrates rich in IgG4(+) cells; a "storiform" fibrosis pattern; and obliterative phlebitis affecting various organs. The disease responds well to corticosteroid treatment, with a second-line therapy involving B-cell-directed immunosuppressive biologic agents. Despite intense studies, the pathogenesis of IgG4-RD remains unclear. The inflammatory infiltrates present in affected tissues contain also multiple polyclonal T and B cells, plasma cells, and - often - eosinophils. Cytokines secreted by type 2 helper T-cells and regulatory T-cells are known to cause B-cell differentiation into IgG4-producing plasma cells. On the other hand, large numbers of IgG4(+) plasma cells can be observed in nonspecific chronic inflammatory conditions, areas adjacent to neoplastic lesions with an inflammatory response, and in autoimmune inflammatory infiltrates. Thus, the fundamental question about the role of IgG4(+) cells in the pathogenesis of inflammation, tissue damage, and fibrosis in IgG4-RD still remains unanswered: does IgG4 stimulate or rather - which is more consistent with its natural properties - play a regulatory function in the inflammatory process?

Clinical features, etiology, and survival in patients with restrictive cardiomyopathy: A single-center experience.

BACKGROUND: Numerous prognostic factors have been proposed for cardiac amyloidosis (CA). The knowledge about other subtypes of restrictive cardiomyopathy (RCM) is scant. AIMS: This study aimed to elucidate the etiology and prognostic factors of RCM as well as assess cardiac biomarkers: high-sensitive troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and soluble suppression of tumorigenicity 2, as mortality predictors in RCM. METHODS: We enrolled 36 RCM patients in our tertiary cardiac department. All patients were screened for CA. Genetic testing was performed in 17 patients without CA. RESULTS: Pathogenic or likely pathogenic gene variants were found in 86% of patients, including 5 novel variants. Twenty patients died, and 4 had a heart transplantation during the study. Median overall survival was 29 months (8-55). The univariate Cox models analysis indicated that systolic and diastolic blood pressure, GDF-15, hs-TnT, NT-proBNP, left ventricular stroke volume, the ratio of the transmitral early peak velocity (E) estimated by pulsed wave Doppler over the early mitral annulus velocity (e'), tricuspid annulus plane systolic excursion, early tricuspid valve annular systolic velocity, the presence of pulmonary hypertension, and pericardial effusion influenced survival (P <0.05). A worse prognosis was observed in patients with GDF-15 >1316 pg/ml, hs-TnT >42 ng/l, NT-proBNP >3383 pg/ml, and pericardial effusion >3.5 mm (Kaplan-Meier analysis, log-rank test, P <0.001). CONCLUSIONS: Genetic testing should be considered in every RCM patient where light-chain amyloidosis has been excluded. Survival remains poor regardless of etiology. Increased concentrations of GDF-15, hs-TNT, NT-proBNP, and pericardial effusion are associated with worse prognosis. Further studies are warranted.

[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.

[Borreliosis--simultaneous Lyme carditis and psychiatric disorders--case report]. / Borelioza--jednoczesne zajecie serca oraz zaburzenia psychiczne--opis przypadku.

Borreliosis is a multisystemic disease transmitted by ticks. Its diagnosis still remains a challenge because of the varied clinical picture and of difficulties in detection of the etiological agent (Borrelia burgdorferi). We report a case of a 53-years-old woman admitted to the Clinic of Cardiology due to life-threatening arhythmias with simultaneous deficits in concentration and memory. A suspicion of borreliosis was driven from the presence of cardiac symptoms as well as of psychiatric and from the case histories of a tick bite. The diagnosis was confirmed both by specific serological test and endomyocardial biopsy which revealed spirochetes. The patient responded to treatment with doxycyclin and ceftriaxone. Cardiologic disorders retreated entirely, while cognitive deficits did only partly.

[Lyme carditis--a bitter lesson or a delayed diagnostic success--a case report]. / Borelioza serca - gorzka lekcja czy spózniony sukces diagnostyczny? Opis przypadku.

Lyme carditis is a well known disorder; however, its diagnosis still remains a challenge because of varied clinical picture, low incidence rate and difficulties in detection of the aetiological agent (Borrelia burgdorferi). We report a case of a 60-year-old man with a 2.5-year history of dilated cardiomyopathy, recurring episodes of acute heart failure and arrhythmias which finally were diagnosed as Lyme carditis. The diagnosis was confirmed by endomyocardial biopsy that revealed spirochetes as well as by serological tests which showed complexed Borrelia antibodies. The patient responded to treatment with ceftriaxone and doxycycline.

Impaired right ventricular function as a predictor of early mortality in patients with light­ chain cardiac amyloidosis assessed in a cardiology department.

INTRODUCTION    Light­chain (AL) amyloidosis is the most common cardiac amyloidosis. Despite progress in treatment, early mortality remains a substantial problem in these patients. OBJECTIVES    The aim of this study was to determine a clinical profile of patients diagnosed with AL amyloidosis in a cardiology department, as well as to define the cut­off point for early mortality and identify predictors of early mortality in this population. PATIENTS AND METHODS    The study included 30 patients (14 women; median age, 61.5 years) with AL amyloidosis confirmed by echocardiography and biopsy of 2 organs. RESULTS    Six patients were diagnosed with stage II amyloidosis according to the Mayo 2004 classification, and 24 patients-with stage III. Early mortality was defined as death during 102 days after diagnosis and was observed in 14 patients. Patients who died earlier were younger and more frequently reported a weight loss of more than 10 kg and orthostatic hypotension than patients who died later. Moreover, they had higher concentrations of high­sensitivity troponin T and N­terminal pro­B­type natriuretic peptide (NT­proBNP) and worse left and right ventricular (RV) contractility. In the Cox models, the age of less than 64 years, NT­proBNP levels exceeding 4968 pg/ml, RV end­diastolic diameter of less than 34 mm, and tricuspid annular plane systolic excursion lower than 13 mm were significant predictors of mortality within 102 days after diagnosis. CONCLUSIONS    We presented the results of the first Polish prospective noninterventional study on AL amyloidosis diagnosed in the cardiology department. We found that patients have advanced disease at the time of diagnosis. Younger age, impaired RV function, and higher concentrations of cardiac markers are predictors of worse prognosis.

[Clinico-pathological collations in borreliosis]. / Konfrontacje kliniczno-morfologiczne w boreliozie.

Borreliosis is an infectious disease caused by spirochetal microorganisms Borrelia burgdorferi transmitted by ticks. Due to versatile clinical symptomatology and many pathogenetic aspects not explained yet, diagnosis of this disease is often very difficult. Borreliosis may affect various human organs and systems such as movement system, nervous system (central and peripheral), skin, heart and vessels. One of the diagnostic methods for detection of microbial organisms in tissues is the histochemical staining by Warthin-Starry. Very important problem connected with this illness is the relationship between borrelial antigens and autoimmunity.