Waldenströmova makroglobulinémie (WM) patří k low-grade B-lymfomům. Je definována přítomností lymfoplazmocytárního lymfomu v kostní dřeni a monoklonálního imunoglobulinu typu IgM (M-IgM) v séru. Příznaky nemoci, anémie a trombocytopenie, mohou souviset s masou patologických buněk, stejně jako systémové zánětlivé projevy (B-symptomy). Velké spektrum symptomů však způsobuje M-IgM. Koncentrace M-IgM u WM nekoreluje s masou patologických buněk. Spektrum poruch způsobených M-IgM je vzhledem k diverzitě patofyziologických mechanizmů a lokalizaci poškození značně široké. Poškození může vzniknout depozicí kompletní molekuly nebo její části ve formě agregátů, amorfních, krystalických, mikrotubulárních či fibrilárních struktur. M-IgM může také pacienta poškozovat autoprotilátkovou aktivitou namířenou proti antigenům vlastních tkání. Dále může M-IgM tvořit imunitní komplexy a aktivovat komplement. Výjimečně může B buněčný klon indukovat tvorbu cytokinů. Proto je velmi obtížené včas rozpoznat symptomatickou formu WM. V této publikaci popisujeme pacientku poškozenou depozity M-IgM a řetězců lambda. Diskuze je zaměřena na přehled všech forem poškození člověka depozity M-IgM, mezi něž patří i popsaný případ.

Waldenström’s macroglobulinaemia (WM) is a low-grade B-cell lymphoproliferative disorder characterised by an immunoglobulin IgM monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic lymphoma. Clinical features may be related to the overall disease burden, such as anaemia, thrombocytopenia, and constitutional inflammatory symptoms, or may be directly attributable to the IgM paraprotein. The concentration of monoclonal IgM can vary widely in WM. There is no direct relationship between the concentration of monoclonal immunoglobulin IgM and bone marrow infiltration. The spectrum of monoclonal immunoglobulin IgM-related disorders is large because of the diversity of involved organs and pathogenic mechanisms. Lesions commonly result from the deposition of all or part of the M-IgM as aggregates, amorphous, crystalline, microtubular, or fibrillar forms. Other mechanisms include autoantibody activity against a tissue antigen, formation of immune complexes, and complement activation. In addition, even a small B-cell clone may absorb biologically active molecules or induce cytokine secretion. In our case report, we describe a female patient with monoclonal IgM and lambda liver deposition and we discuss the frequency and variety of disorders caused by deposition of monoclonal IgM and free light chain.

• Klíčová slova
• imunokomplexy,
• MeSH
• amyloid imunologie   klasifikace   MeSH
• amyloidóza diagnóza   imunologie   klasifikace   patologie   MeSH
• hepatomegalie etiologie   imunologie   MeSH
• imunoglobulin M imunologie   krev   škodlivé účinky   MeSH
• krevní nemoci diagnóza   etiologie   krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Waldenströmova makroglobulinemie * diagnostické zobrazování   diagnóza   imunologie   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation (SOT). However, there is no consensus on PTLD screening methods. Gammopathies (GP), which occur in 10-25% of SOT recipients, have been linked to subsequent development of PTLD. Therefore, GP detection methods, such as serum protein electrophoresis (SPE), serum protein immunofixation (SIFE), urine protein immunofixation (UIFE) and the quantitative measurement of serum free light chains (SFLC) are candidate methods for PTLD screening. OBJECTIVE: We aimed to assess the frequency of PTLD and GP, association of GP with subsequent PTLD, allograft loss or death and the diagnostic performance of SPE/SIFE in PTLD screening. The main objective was to explore, whether GP detection methods can be used to enhance the efficiency of PTLD screening and to formulate a concise algorithm for posttransplantation (post-Tx) follow-up. METHODS: We performed a cohort study on 1677 SOT recipients with SPE/SIFE data who underwent kidney, liver, heart, pancreas, Langerhans islets or multiple organ transplantation at the Institute of Clinical and Experimental Medicine between 1966 and 2015. The median (IQR) of follow-up time was 8.0 (4.0-12.0) years. RESULTS: The frequencies of PTLD and GP in SOT recipients were 2.8% and 6.4%, respectively. The frequencies of transient GP, GP of undetermined significance and malignant GP were 33%, 63% and 4% respectively. The median time between SOT and GP detection was 2.0 (interquartile range 1.0-7.0) years. GP was associated with a significantly higher risk of PTLD, allograft loss and death, with hazard ratios (95% confidence intervals) of a 6.06 (2.51-14.64), 2.61 (1.49-4.6) and 1.99 (1.2-3.3), respectively. Additionally, GP was associated with 2.98-fold increased risk of allograft loss in kidney transplant patients. SPE diagnostic sensitivity and specificity for PTLD were 14.8% and 93.9%, respectively. PTLD was diagnosed more often and earlier if SPE/SIFE was included in the post-Tx follow-up. CONCLUSIONS: GP after SOT is associated with a high risk of PTLD, allograft loss and poor survival. The combination of SPE, SIFE, SFLC and UIFE is optimal for GP detection. These methods aid in identifying patients who are at risk for PTLD or allograft damage and should be included in regular post-Tx follow-up.

• MeSH
• algoritmy MeSH
• analýza přežití MeSH
• dospělí MeSH
• homologní transplantace MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• paraproteinemie diagnóza   epidemiologie   mortalita   MeSH
• plošný screening MeSH
• pooperační komplikace diagnóza   epidemiologie   mortalita   MeSH
• rejekce štěpu diagnóza   epidemiologie   mortalita   MeSH
• riziko MeSH
• transplantace orgánů * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Úvod: Hypereosinofilní syndrom (HES) představuje heterogenní skupinu onemocnění definovaných nápadnou hypereosinofilií (1,5× 109/l), která přetrvává po více než šest měsíců a je provázena infiltrací a poškozením orgánů. Postižení srdce u HES je běžné a je spojeno s významnou morbiditou a mortalitou. Abychom ilustrovali aktuální možnosti diagnostiky a léčby tohoto syndromu, popisujeme tři případy HES s postižením srdce, nedávno diagnostikované na našem pracovišti. Popis případů: Přinášíme sérii tří kasuistik HES s postižením srdce a klinickým obrazem zahrnujícím intrakardiální trombózu. V jednom z případů byla příčinou FIP1L1-PDGFRA-pozitivní myeloproliferace, úspěšně léčená imatinibem. Ve všech případech byly podávány kortikosteroidy a byla zavedena perorální antikoagulace antagonisty vitaminu K, a to s příznivými klinickými výsledky. Závěry: Ačkoli HES s postižením srdce je vzácný, může mít závažné klinické následky a musí být diagnostikován včas. Důležitým následným krokem je pečlivá diferenciální diagnostika hypereosinofilie a její cílená léčba.

Introduction: Hypereosinophilic syndrome (HES) is a heterogeneous group of diseases defined by marked hyperesonofilia (1.5× 109/l) that persists more than 6 months with organ infiltration and damage. Cardiac involvement in HES is common and is associated with significant morbidity and mortality. To illustrate contemporary diagnostic and therapeutic methods, we reviewed three cases of HES with cardiac involvement, recently diagnosed in our institution. Description of cases: We present a series of three cases of HES with cardiac involvement and clinical presentation in the form of intracardiac thrombosis. One of these cases was caused by FIP1L1-PDGFRA positive myeloproliferation and successfully treated with imatinib. All cases received corticosteroids and oral anticoagulation with vitamin K antagonists with favourable clinical outcomes. Conclusions: Although HES with cardiac involvement is a rare condition, it may have severe clinical consequences and needs to be diagnosed early. Subsequent important step is careful differential diagnosis of hypereosinophilia and its targeted treatment.

• MeSH
• biopsie metody   MeSH
• dospělí MeSH
• echokardiografie MeSH
• eozinofilie komplikace   MeSH
• hypereozinofilní syndrom * diagnostické zobrazování   patofyziologie   patologie   MeSH
• imunohistochemie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• myokarditida diagnostické zobrazování   etiologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

OBJECTIVES: To assess the timelines of serum free light chain (sFLC) concentrations and the kappa/lambda light chain (K/L) ratio in heart transplant (HTX) recipients. To analyze the performance of serum protein electrophoresis (SPE), serum immunofixation (sIFE) and sFLC measurements for gammopathy detection following a HTX. METHODS: A total of 96 patients who underwent a HTX were analyzed during a two-year follow-up period. The relevant clinical data were obtained from patient medical records. SPE, sIFE and sFLC methods were used for the detection of free light chain and intact immunoglobulin gammopathies at 4 time points after HTX. RESULTS: A statistically significant decrease in sFLC K and L (a decrease of 39.1% and 27.6%, respectively, when compared to pretransplant values) was found 9months after the HTX (p<0.001, Friedman test). We detected SPE or sIFE abnormalities in 23 (8.4%) samples, and sFLC K/L ratio abnormalities in 34 (12.4%) samples. All of the K/L ratio abnormalities had normal SPE/sIFE values, and 19% of the findings were persistent. CONCLUSIONS: A significant and consistent dynamics in the sFLC concentration was found in the HTX patients during a 2-year follow-up period, which reflected changes in the immunosuppressant dosage. A remarkable number of monoclonal and polyclonal gammopathies was identified with some persistent abnormalities, using the SPE/sIFE and sFLC methods. Some of the detected abnormalities, which might possess a higher risk for PTLD if interpreted according to common practice in nonTX patients can only be detected by sFLC methods.

• MeSH
• dospělí MeSH
• imunoglobuliny - kappa-řetězce krev   MeSH
• imunoglobuliny - lambda-řetězce krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• senioři MeSH
• transplantace srdce * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Constitutional translocations between sex chromosomes are rather rare in humans with breakpoints at Xp11 and Yq11 as the most frequent. Breakpoints on the short arm of the Y chromosome form one subgroup of t(X;Y), giving rise to a derived chromosome with the centromeres of both the X and Y chromosomes, dic(X;Y). Here, we report a rare congenital chromosomal aberration, 46,X,dic(X;Y)(p22.33;p11.32)[20]/45,X[10], in an adult male. CASE PRESENTATION: Primary myelofibrosis, a malignant haematological disease, was diagnosed in a 63-year-old man following liver transplantation after hepatocellular carcinoma. By the analysis of the bone marrow sample, the karyotype 46,X,dic(X;Y)(p22.33;p11.32) was detected in all the mitoses analysed and verified with multicolour fluorescence in situ hybridization (mFISH). A cytogenetic examination of stimulated peripheral blood cells revealed the constitutional karyotype 46,X,dic(X;Y)(p22.33;p11.32)[20]/45,X[10]. The cell line 45,X was confirmed with FISH in 35 % of interphase nuclei. The SRY locus was present on the dicentric chromosome. A CGH/SNP array (Illumina) revealed a gain of 153,7 Mbp of the X chromosome and a 803-kbp microdeletion (including the SHOX gene), which were also confirmed with FISH. SHOX encodes a transcriptional factor that regulates the growth of the long bones. The deletion of the SHOX gene together with the Madelung deformity of the forearm and the short stature of the proband led to a diagnosis of Léri-Weill dyschondrosteosis (LWD). The gain of almost the whole X chromosome (153,7 Mbp) was considered a variant of Klinefelter syndrome (KS). The levels of gonadotropins and testosterone were consistent with gonadal dysfunction. A malformation of the right external ear was detected. CONCLUSIONS: We have reported a structural aberration of the sex chromosomes, dic(X;Y)(p22.33;p11.32). The related genomic imbalance is associated with two known hereditary syndromes, LWD and a KS variant, identified in our proband at an advanced age. Because the breakpoints did not involve cancer genes, we inferred that the two malignancies in the proband were not caused by this abnormality. The possible influence of SHOX haploinsufficiency on the growth regulation of auricular chondrocytes is discussed.

• Publikační typ
• časopisecké články MeSH