Publications by authors named "Izabela Drozdz"

7 Publications

  • Page 1 of 1

Clinical heterogeneity among pediatric patients with autoimmune type 1 diabetes stratified by immunoglobulin deficiency.

Pediatr Diabetes 2021 Apr 10. Epub 2021 Apr 10.

Department of Pediatrics, Oncology, and Hematology, Medical University of Łódź, Łódź, Poland.

Background: Type 1 diabetes (T1D) may coexist with primary immunodeficiencies, indicating a shared genetic background.

Objective: To evaluate the prevalence and clinical characteristics of immunoglobulin deficiency (IgD) among children with T1D.

Methods: Serum samples and medical history questionnaires were obtained during routine visits from T1D patients aged 4-18 years. IgG, IgA, IgM, and IgE were measured by nephelometry and enzyme-linked immunosorbent assay (ELISA). IgG and IgM deficiency (IgGD, IgMD) were defined as IgG/IgM >2 standard deviations (SD) below age-adjusted mean. IgE deficiency was defined as IgE <2 kIU/L. IgA deficiency (IgAD) was defined as IgA >2 SD below age-adjusted mean irrespective of other immunoglobulin classes (absolute if <0.07 g/L, partial otherwise) and as selective IgAD when IgA >2 SD below age-adjusted mean with normal IgG and IgM (absolute if <0.07 g/L, partial otherwise).

Results: Among 395 patients (53.4% boys) with the median age of 11.2 (8.4-13.7) and diabetes duration 3.6 (1.1-6.0) years, 90 (22.8%) were found to have hypogammaglobulinemia. The IgGD and IgAD were the most common each in 40/395 (10.1%). Complex IgD was found in seven patients. Increased odds of infection-related hospitalization (compared to children without any IgD) was related to having any kind of IgD and IgAD; OR (95%CI) = 2.1 (1.2-3.7) and 3.7 (1.8-7.5), respectively. Furthermore, IgAD was associated with having a first-degree relative with T1D OR (95%CI) = 3.3 (1.4-7.6) and suffering from non-autoimmune comorbidities 3.3 (1.4-7.6), especially neurological disorders 3.5 (1.2-10.5).

Conclusions: IgDs frequently coexist with T1D and may be associated with several autoimmune and nonimmune related disorders suggesting their common genetic background.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pedi.13208DOI Listing
April 2021

The Prognostic Value of Whole-Blood PSMB5, CXCR4, POMP, and RPL5 mRNA Expression in Patients with Multiple Myeloma Treated with Bortezomib.

Cancers (Basel) 2021 Feb 25;13(5). Epub 2021 Feb 25.

Department of Hematology, Medical University of Lodz, 93-510 Lodz, Poland.

Proteasome inhibitors, like bortezomib, play a key role in the treatment of multiple myeloma (MM); however, most patients eventually relapse and eventually show multiple drug resistance, and the molecular mechanisms of this resistance remain unclear. The aim of our study is to assess the expression of previously described genes that may influence the resistance to bortezomib treatment at the mRNA level (, , , , , , , and ) and prognosis of MM patients. mRNA expression was determined in 73 MM patients treated with bortezomib-based regimens (30 bortzomib-sensitive and 43 bortezomib-refractory patients) and 11 healthy controls. was significantly down-regulated in multiple myeloma patients as compared with healthy controls. Moreover, POMP was significantly up-regulated in MM patients refractory to bortezomib-based treatment. In multivariate analysis, high expression of and and autologous stem cell transplantation were independent predictors of progression-free survival, and high expression of and was associated with shorter overall survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13050951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956525PMC
February 2021

The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients.

Cancers (Basel) 2020 Sep 9;12(9). Epub 2020 Sep 9.

Department of Hematology, Medical University of Lodz, 93-510 Lodz, Poland.

Bortezomib is the first-in-class proteasome inhibitor, commonly used in the treatment of multiple myeloma (MM). The mechanisms underlying acquired bortezomib resistance in MM are poorly understood. Several cell-free miRNAs have been found to be aberrantly regulated in MM patients. The aim of this pilot study was to identify a blood-based miRNA signature that predicts bortezomib-based therapy efficacy in MM patients. Thirty MM patients treated with bortezomib-based regimens were studied, including 19 with refractory disease and 11 who were bortezomib sensitive. Serum miRNA expression patterns were identified with miRCURY LNA miRNA miRNome PCR Panels I+II (Exiqon/Qiagen). Univariate analysis found a total of 21 miRNAs to be differentially expressed in patients with MM according to bortezomib sensitivity. Multivariate logistic regression was created and allowed us to discriminate refractory from sensitive patients with a very high AUC of 0.95 (95%CI: 0.84-1.00); sensitivity, specificity and accuracy were estimated as 0.95, 0.91, and 0.93. The model used expression of 3 miRNAs: miR-215-5p, miR-181a-5p and miR-376c-3p. This study is the first to demonstrate that serum expression of several miRNAs differs between patients who are bortezomib refractory and those who are sensitive which may prove useful in studies aimed at overcoming drug resistance in MM treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12092569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565855PMC
September 2020

Cytokine and Chemokine Profile in Patients with Multiple Myeloma Treated with Bortezomib.

Mediators Inflamm 2020 6;2020:1835836. Epub 2020 Jun 6.

Department of Hematology, Medical University of Lodz, Poland.

The aim of the study was to determine the levels of selected cytokines and chemokines in the serum of multiple myeloma (MM) patients treated with bortezomib-based regimens. A total of 71 MM patients were examined: 41 with primary refractory disease (17) or early relapse (28), and 30 who were bortezomib sensitive with no progression for at least six months. Patients who demonstrated CR or PR after bortezomib-based therapies longer than six months after treatment discontinuation were designated bortezomib sensitive. Serum cytokine levels were assayed with Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay on the MAGPIX Multiplex Reader and the Bio-Plex® 200 System (Bio-Rad). Higher levels of MIP-1 and lower levels of MIP-1 and IL-9 were associated with better responses to bortezomib-based treatment, and higher levels of IL-1ra and IL-8 were associated with bone involvement. MCP-1 was elevated in patients with hemoglobin < 10 g/dl compared to those without anemia. The levels of IL-8, MIP-1, and TNF- were significantly higher in patients with renal insufficiency. Only MIP-1 was elevated in patients with hypercalcemia compared to patients with normal calcium levels. In conclusion, distinct cytokines are involved in the pathogenesis of MM and may play a prominent role in the prediction of treatment response. However, a single measurement of serum cytokines should be interpreted with caution and further studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/1835836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294367PMC
June 2021

Drug resistance in multiple myeloma.

Cancer Treat Rev 2018 Nov 4;70:199-208. Epub 2018 Sep 4.

Department of Hematology, Medical University of Lodz, Lodz, Poland. Electronic address:

Multiple myeloma (MM, plasma cell myeloma) is a malignant hematologic disease characterized by the clonal proliferation of malignant plasma cells. The treatment of MM has changed dramatically in recent years, with the introduction of new drugs into therapeutic strategies, both in the front line setting and in relapsed refractory disease. However, most patients eventually relapse and often demonstrate multiple drug resistance. Therefore there is still an urgent and unmet need to define the molecular mechanisms of resistance for available drugs in order to enhance the use of existing treatments and design more effective therapies. Genetic abnormalities are well known to play a central role in MM resistance to available drugs, and epigenetic aberrations mainly affecting the patterns of DNA methylation and histone modifications of genes, especially tumor suppressors, can be involved in the resistance mechanism. Moreover, defects in the mechanisms of apoptosis, senescence and DNA repair could also contribute to drug resistance. In addition, mutations or alterations in the expression of the drug target can influence response to therapy. Achieving a better understanding of the pathways and protein expression involved in MM drug resistance and the development of novel therapeutic strategies are important goals for further progress in the treatment of MM. This review gives a critical overview of the role of cellular, microenvironmental and molecular mechanisms of drug resistance in MM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctrv.2018.09.001DOI Listing
November 2018

Chromosome 18q deletion syndrome with autoimmune diabetes mellitus: putative genomic loci for autoimmunity and immunodeficiency.

Pediatr Diabetes 2016 Mar 18;17(2):153-9. Epub 2014 Nov 18.

Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.

A girl with 18q deletion syndrome was diagnosed with autoimmune diabetes mellitus and Hashimoto's thyroiditis at the age of 3 yr. In addition, the girl suffered from recurrent infections due to immunoglobulin A and IgG4 deficiency. She was also found to have CD3+CD4+FoxP3+, CD3+CD4+FoxP3+CD25+, and CD3+CD4+CD25+CD127 regulatory T cells deficiency. The exceptional coincidence of the two autoimmune disorders occurring at an early age, and associated with immune deficiency, implies that genes located on deleted 19.4 Mbp region at 18q21.32-q23 (chr18:58,660,699-78,012,870) might play a role in the pathogenesis of autoimmunity leading to β cell destruction and diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pedi.12235DOI Listing
March 2016

Switching to sulphonylureas in children with iDEND syndrome caused by KCNJ11 mutations results in improved cerebellar perfusion.

Diabetes Care 2013 Aug 5;36(8):2311-6. Epub 2013 Mar 5.

Department of Paediatrics, Oncology, Haematology, and Diabetology, Medical University of Lodz, Lodz, Poland.

Objective: Activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the KATP channel, result in permanent neonatal diabetes mellitus. They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). Sulphonylurea (SU) treatment is reported to alleviate both the neurologic symptoms and diabetes in such cases. The study aimed to establish the magnitude and functional basis of the effect of SUs on the neurologic phenotype in children with iDEND using neuroimaging before and after insulin replacement with glibenclamide.

Research Design And Methods: To localize and quantify the effect of glibenclamide administration, we performed single-photon emission computed tomography in seven patients with different mutations in KCNJ11. In five patients, measurements before and after initiation of SU treatment were performed. RESULTS Significant changes in single-photon emission computed tomography signal intensity after transfer to SU therapy were restricted to the cerebellum, consistent with previous data showing high Kir6.2 expression in this brain region. Cerebellar perfusion improved for both left (P = 0.006) and right (P = 0.01) hemispheres, with the mean improvement being 26.7 ± 7.1% (n = 5). No patients showed deterioration of cerebellar perfusion on SU therapy. Electrophysiological studies revealed a good correlation between the magnitude of KATP channel dysfunction and the clinical phenotype; mutant channels with the greatest reduction in adenosine 5'-triphosphate inhibition were associated with the most severe neurologic symptoms.

Conclusions: We conclude it is likely that at least some of the beneficial effects of SU treatment on neurodevelopment in iDEND patients result from improved cerebellar perfusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc12-2166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714477PMC
August 2013