Donor genetic determinant of thymopoiesis, rs2204985, and stem cell transplantation outcome in a multipopulation cohort.

BACKGROUND: A genetic polymorphism, rs2204985, has been reported to be associated with the diversity of T-cell antigen receptor repertoire and TREC levels, reflecting the function of the thymus. As the thymus function can be assumed to be an important factor regulating the outcome of stem cell transplantation (SCT), it was of great interest that rs2204985 showed a genetic association to disease-free and overall survival in a German SCT donor cohort. Tools to predict the outcome of SCT more accurately would help in risk assessment and patient safety. OBJECTIVE: To evaluate the general validity of the original genetic association found in the German cohort, we determined genetic associations between rs2204985 and the outcome of SCT in 1,473 SCT donors from four different populations. STUDY DESIGN: Genetic associations between rs2204985 genotype AA versus AG/GG and overall survival (OS) and disease-free survival (DFS) in 1,473 adult, allogeneic SCT from Finland, the United Kingdom, Spain, and Poland were performed using the Kaplan-Meier analysis and log-rank tests. We adjusted the survival models with covariates using Cox regression. RESULTS: In unrelated SCT donors (N = 425), the OS of genotype AA versus AG/GG had a trend for a similar association (p = 0.049, log-rank test) as previously reported in the German cohort. The trend did not remain significant in the Cox regression analysis with covariates. No other associations were found. CONCLUSION: Weak support for the genetic association between rs2204985, previously also associated with thymus function, and the outcome of SCT could be found in a cohort from four populations.

Association of MICA and NKG2D genetic variants with disease susceptibility and outcome of anti-TNF therapy in patients with axial spondyloarthritis.

OBJECTIVES: The disruption of the NKG2D-MICA axis can induce an enhanced immune response and promote autoimmune processes during axial spondyloarthritis (axSpA) pathogenesis. We aimed to investigate potential relationships between selected single nucleotide polymorphisms within the MICA and NKG2D genes and disease susceptibility and clinical parameters in axSpA patients treated with TNF inhibitors. METHODS: Genotyping of MICA rs1051792 and NKG2D rs1154831, rs1049174, and rs2255336 was performed in 163 axSpA patients and 234 healthy controls using a real-time PCR method. RESULTS: MICA rs1051792 A allele was more common in patients than in controls (p<0.0001). Patients with the AA genotype showed greater disease activity score (BASDAI) after three (p=4×10-4) and six (p=0.032) months of treatment compared to G carriers. After three months of therapy with anti-TNFs, the MICA AA homozygosity occurred more often in non-responsive or moderately responsive patients than good responders with the same genotype (p=1×10-4). Additionally, patients bearing the NKG2D rs1154831 CC genotype demonstrated lower BASDAI scores (p=0.035) and were significantly more common among subjects with a good outcome (p=0.004) after six months of treatment. CONCLUSIONS: These results suggest that MICA and NKG2D gene polymorphisms may be biomarkers associated with disease susceptibility and clinical outcomes after anti-TNF therapy in axSpA patients and imply a rather less favourable effect of the MICA A and NKG2D G genetic variants.

Current status and perspectives of the quality system in histocompatibility laboratories in Poland.

Allogeneic transplantation is a multi-step process involving many clinicians and laboratory personnel working together to achieve a common goal-to maximize the recipients' chance of survival and to improve their quality of life. One of the key elements of the process is to ensure high quality, accuracy, and reliability of histocompatibility testing. This manuscript presents: the development and organizational principles of the national system of supervision and control of histocompatibility laboratories in Poland, problems faced by these laboratories, availabe proficiency testing schemes, as well as suggestions and prospects for the future raised by members of the Polish histocompatibility community.

Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells.

Transplantation of hematopoietic stem cells (HSCT) is a procedure commonly used in treatment of various haematological disorders which is associated with significantly improved survival rates. However, one of its drawbacks is the possibility of development of post-transplant complications, including acute and chronic graft-versus-host disease (GvHD) or CMV infection. Various studies suggested that NK cells and their receptors may affect the transplant outcome. In the present study, patients and donors were found to significantly differ in the distribution of the NKG2A rs7301582 genetic variants - recipients carried the C allele more often than their donors (0.975 vs 0.865, p<0.0001). Increased soluble HLA-E (sHLA-E) levels detected in recipients' serum 30 days after transplantation seemed to play a prognostic and protective role. It was observed that recipients with higher sHLA-E levels were less prone to chronic GvHD (11.65 vs 6.33 pg/mL, p=0.033) or more severe acute GvHD grades II-IV (11.07 vs 8.04 pg/mL, p=0.081). Our results also showed an unfavourable role of HLA-E donor-recipient genetic incompatibility in CMV infection development after transplantation (OR=5.92, p=0.014). Frequencies of NK cells (both CD56dim and CD56bright) expressing NKG2C were elevated in recipients who developed CMV, especially 30 and 90 days post-transplantation (p<0.03). Percentages of NKG2C+ NK cells lacking NKG2A expression were also increased in these patients. Moreover, recipients carrying a NKG2C deletion characterized with decreased frequency of NKG2C+ NK cells (p<0.05). Our study confirms the importance of NK cells in the development of post-transplant complications and highlights the effect of HLA-E and NKG2C genetic variants, sHLA-E serum concentration, as well as NKG2C surface expression on transplant outcome.

Pro- and anti-inflammatory cytokines and growth factors in patients undergoing in vitro fertilization procedure treated with prednisone.

Embryo implantation is a key moment in pregnancy. Abnormal production of pro- and anti-inflammatory cytokines, their receptors and other immune factors may result in embryo implantation failure and pregnancy loss. The aim of this study was to determine the profile of selected pro- and anti-inflammatory factors in the blood plasma of patients undergoing in vitro fertilization (IVF) and control women who achieved pregnancy after natural conception. The examined patients were administered steroid prednisone. We present results concern the plasma levels of IFN-ɣ, BDNF, LIF, VEGF-A, sTNFR1 and IL-10. We found that IVF patients receiving steroids differed significantly from patients who were not administered such treatment in terms of IFN-γ and IL-10 levels. Moreover, IVF patients differed in secretion of all tested factors with the fertile controls. Our results indicated that women who secrete at least 1409 pg/ml of sTNFR1 have a chance to become pregnant naturally and give birth to a child, while patients after IVF must achieve a concentration of 962.3 pg/ml sTNFR1 in blood plasma for successful pregnancy. In addition, IVF patients secreting VEGF-A above 43.28 pg/ml have a greater risk of miscarriage or a failed transfer in comparison to women secreting below this value. In conclusion, fertile women present a different profile of pro- and anti-inflammatory cytokines, and growth factors compared to patients with recurrent implantation failure (RIF).

Telomere length and hTERT genetic variants as potential prognostic markers in multiple myeloma.

Telomere dysfunction is a notable event observed in many cancers contributing to their genomic instability. A major factor controlling telomere stability is the human telomerase reverse transcriptase catalytic subunit (hTERT). Telomere shortening has been observed in multiple myeloma (MM), a plasma cell malignancy with a complex and heterogeneous genetic background. In the present study, we aimed to analyse telomere length and hTERT genetic variants as potential markers of risk and survival in 251 MM patients. We found that telomere length was significantly shorter in MM patients than in healthy individuals, and patients with more advanced disease (stage III according to the International Staging System) had shorter telomeres than patients with less advanced disease. MM patients with hTERT allele rs2736100 T were characterized with significantly shorter progression-free survival (PFS). Moreover, allele rs2736100 T was also found to be less common in patients with disease progression in response to treatment. hTERT rs2853690 T was associated with higher haemoglobin blood levels and lower C-reactive protein. In conclusion, our results suggest that telomere length and hTERT genetic variability may affect MM development and can be potential prognostic markers in this disease.

Complex interactions of cellular players in chronic Graft-versus-Host Disease.

Chronic Graft-versus-Host Disease is a life-threatening inflammatory condition that affects many patients after allogeneic hematopoietic stem cell transplantation. Although we have made substantial progress in understanding disease pathogenesis and the role of specific immune cell subsets, treatment options are still limited. To date, we lack a global understanding of the interplay between the different cellular players involved, in the affected tissues and at different stages of disease development and progression. In this review we summarize our current knowledge on pathogenic and protective mechanisms elicited by the major involved immune subsets, being T cells, B cells, NK cells and antigen presenting cells, as well as the microbiome, with a special focus on intercellular communication of these cell types via extracellular vesicles as up-and-coming fields in chronic Graft-versus-Host Disease research. Lastly, we discuss the importance of understanding systemic and local aberrant cell communication during disease for defining better biomarkers and therapeutic targets, eventually enabling the design of personalized treatment schemes.

Chronic inflammatory demyelinating polyradiculoneuropathy in patients with diabetes mellitus - treatment with intravenous immunoglobulins: A systematic review.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease, but it is one of the most common inflammatory neuropathies in the population. It is particularly common among patients with diabetes mellitus. This raises many problems, both with the differential diagnosis of diabetic and inflammatory neuropathy, as well as the choice of treatment. Intravenous immunoglobulin (IVIG) is one of the therapeutic options. There is evidence for the effectiveness of IVIG in treating about two-thirds of patients. However, no review has been published to date systematising studies evaluating the response to IVIG treatment in patients with CIDP and coexisting diabetes. METHODS: The present study is based on the PRISMA statement and is registered at PROSPERO (CRD42022356180). The study included searches of the databases of MEDLINE, ERIC, CINAHL Complete, Academic Search Ultimate and Health Source: Nursing/Academic Edition, finally including seven original papers evaluating a total of 534 patients in the review. The main inclusion criteria were the presence of a group of patients with CIDP and comorbid diabetes in the study. RESULTS: The systematic review showed a lower efficacy of IVIG treatment among patients with coexisting diabetes compared with idiopathic CIDP (61 % vs 71 %). In addition, the presence of conduction blocks on neurography and shorter disease duration proved to be significant factors improving response to treatment. CONCLUSIONS: Current scientific data do not allow for strong recommendations on the choice of treatment for CIDP. A randomised, multicentre study evaluating the efficacy of different therapeutic approaches to this disease entity needs to be planned.

The impact of NKG2A and NKG2D receptors and HLA-E and MICA ligands polymorphisms on post-transplant complications after paediatric allogeneic HSCT: a single-centre experience.

Introduction: Natural Killer cells are the first subpopulation of lymphocytes that reconstitute after allogeneic haematopoietic stem cell transplantation (HSCT). Their activity is regulated by various receptor-ligand interactions, including stimulation of the activating NKG2D receptor by the MICA molecule, and inhibitory NKG2A receptor interacting with the HLA-E. In this study the research effort focused on the effect of selected NKG2A and NKG2D receptors and their ligands (HLA-E and MICA molecules) polymorphisms that may affect the pathomechanisms of post-transplant complications after HSCT in children. Methods: One hundred donor-recipient pairs from a single paediatric transplantation centre were investigated. Altogether six single nucleotide substitutions (NKG2A rs7301582; NKG2D rs1049174, rs1154831; HLA-E rs1264457; MICA rs1051792, rs1063635) were genotyped, and the influence of polymorphisms was analysed on acute and chronic graft-versus-host disease (GvHD), cytomegalovirus (CMV) infection incidence, disease relapse and survival. Results: The distribution of the evaluated polymorphisms did not differ between patients and their donors. The results showed a significant influence of HLA-E rs1264457 polymorphism in patients' HLA-E*01:01 allele, which was associated with increased risk of CMV infection (p = 0.050), especially in children positive for CMV IgG before transplantation (p = 0.001). Furthermore, the effect of HLA-E*01:01 allele on CMV infections was more evident in children above the age of 7 years (p = 0.031). Strong tendencies (0.05 < p < 0.10) towards association with the risk of acute GvHD were also observed for the NKG2A or MICA polymorphisms of the recipients. In addition, NKG2D rs1154831 AA and MICA rs1063635 GG might play a protective role as they were not present in any recipient who died after transplantation. Conclusion: In summary, there is emerging evidence that genotyping results of NKG2 receptors and their ligands, may have prognostic value for the outcome of paediatric allogeneic HSCT, but more extensive studies performed on larger groups of donors and transplant recipients are required to confirm these observations.

Activating NKG2C Receptor: Functional Characteristics and Current Strategies in Clinical Applications.

The interest in NK cells and their cytotoxic activity against tumour, infected or transformed cells continuously increases as they become a new efficient and off-the-shelf agents in immunotherapies. Their actions are balanced by a wide set of activating and inhibitory receptors, recognizing their complementary ligands on target cells. One of the most studied receptors is the activating CD94/NKG2C molecule, which is a member of the C-type lectin-like family. This review is intended to summarise latest research findings on the clinical relevance of NKG2C receptor and to examine its contribution to current and potential therapeutic strategies. It outlines functional characteristics and molecular features of CD94/NKG2C, its interactions with HLA-E molecule and presented antigens, pointing out a key role of this receptor in immunosurveillance, especially in the human cytomegalovirus infection. Additionally, the authors attempt to shed some light on receptor's unique interaction with its ligand which is shared with another receptor (CD94/NKG2A) with rather opposite properties.

The Influence of Comorbidities on Chemokine and Cytokine Profile in Obstructive Sleep Apnea Patients: Preliminary Results.

INTRODUCTION: Obstructive sleep apnea (OSA) is frequently associated with a chronic inflammatory state and cardiovascular/metabolic complications. The aim of this study was to evaluate the influence of certain comorbidities on a panel of 45 chemokines and cytokines in OSA patients with special regard to their possible association with cardiovascular diseases. MATERIAL AND METHODS: This cross-sectional study was performed on 61 newly diagnosed OSA patients. For the measurement of the plasma concentration of chemokines and cytokines, the magnetic bead-based multiplex assay for the Luminex® platform was used. RESULTS: In the patients with concomitant COPD, there were increased levels of pro-inflammatory cytokines (CCL11, CD-40 ligand) and decreased anti-inflammatory cytokine (IL-10), while in diabetes, there were increased levels of pro-inflammatory cytokines (IL-6, TRIAL). Obesity was associated with increased levels of both pro-inflammatory (IL-13) and anti-inflammatory (IL-1RA) cytokines. Hypertension was associated with increased levels of both pro-inflammatory (CCL3) and anti-inflammatory (IL-10) cytokines. Increased daytime pCO2, low mean nocturnal SaO2, and the oxygen desaturation index were associated with increased levels of pro-inflammatory cytokines (CXCL1, PDGF-AB, TNF-α, and IL-15). CONCLUSIONS: In OSA patients with concomitant diabetes and COPD, elevated levels of certain pro-inflammatory and decreased levels of certain anti-inflammatory cytokines may favor the persistence of a chronic inflammatory state with further consequences. Nocturnal hypoxemia, frequent episodes of desaturation, and increased daytime pCO2 are factors contributing to the chronic inflammatory state in OSA patients.

Differential expression of miRNAs from extracellular vesicles in chronic graft-versus-host disease: A preliminary study.

BACKGROUND: Chronic graft-versus-host disease (cGvHD) is a complex disorder that typically manifests after allogeneic hematopoietic stem cell transplantation (HSCT). It is a major cause of non-relapse mortality, which makes finding biomarkers associated with its occurrence a priority. Recent studies increasingly indicate that microRNAs (miRNAs, short regulatory RNA molecules) can be used as biomarkers of various disorders. They can circulate in patients' bodies encapsulated within extracellular vesicles (EVs). OBJECTIVES: To identify miRNAs associated with the occurrence of cGvHD in EVs isolated from the plasma of patients after allogeneic HSCT. MATERIAL AND METHODS: We performed global miRNA expression profiling in a pilot cohort of 3 cGvHD cases and 4 non-cGvHD patients without disease symptoms 90 days after the transplantation (control group). RESULTS: The 2 groups were naturally clustered according to their miRNA profiles using unsupervised hierarchical clustering analysis. We identified 3 miRNAs that were differentially expressed in the cGvHD patients compared to the non-cGvHD patients. The levels of hsa-miR-630 and hsa-miR-374b-5p were lower in the cGvHD patients: 4.1-fold (p = 0.002) and 2.7-fold (p = 0.044), respectively. In contrast, the levels of hsa-miR-29c-3p were 5.8-fold higher (p = 0.004). CONCLUSIONS: Our results suggest that miRNA profiles from plasma EVs may act as markers of cGvHD onset.

Genetic Variants of the TERT Gene and Telomere Length in Obstructive Sleep Apnea.

Introduction: Obstructive sleep apnea (OSA) is a worldwide breathing disorder that has been diagnosed globally in almost 1 billion individuals aged 30−69 years. It is characterized by repeated upper airway collapses during sleep. Telomerase reverse transcriptase (TERT) is involved in the prevention of telomere shortening. This prospective, observational study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) of TERT and the severity of OSA, taking into account hypertension and diabetes prevalence. Methods: A total of 149 patients with OSA were diagnosed using one-night video-polysomnography based on the American Academy of Sleep Medicine guidelines. The TERT SNPs and telomere length (TL) were detected using real-time quantitative polymerase chain reaction. Results: Statistical analysis showed that there is no relationship between the rs2853669 and rs2736100 polymorphisms of TERT, and the severity of OSA (p > 0.05). Moreover, no relationship between TL and the severity of OSA was observed. The G allele in the locus of rs2736100 TERT was associated with hypertension prevalence and was more prevalent in hypertensives patients (46.00% vs. 24.49%, p = 0.011). The prevalence of hypertension was higher in patients with the C allele in the locus of rs2853669 than in patients without this allele (50.79% vs. 30.23%, p = 0.010). Moreover, a lower prevalence of diabetes was observed in homozygotes of rs2736100 TERT than in heterozygotes (5.63% vs. 15.38%, p = 0.039). Conclusion: This study showed no relationship between OSA and TERT SNPs. However, SNPs of the TERT gene (rs2736100 and rs2853669) were found to affect arterial hypertension and diabetes prevalence.

Th2 Cytokines (Interleukin-5 and -9) Polymorphism Affects the Response to Anti-TNF Treatment in Polish Patients with Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is an inflammatory disease that belongs to the spondyloarthritis family. IL-5 and IL-9 belong to the group of Th2 cytokines of anti-inflammatory nature. Polymorphisms in their coding genes have been so far associated with various inflammatory diseases, but there are no reports regarding their involvement in AS pathogenesis to date. The purpose of the study was to investigate relationships between IL5 and IL9 genetic variants with AS susceptibility, clinical parameters as well as response to therapy with TNF inhibitors. In total 170 patients receiving anti-TNF therapy and 218 healthy controls were enrolled in the study. The genotyping of IL5 rs2069812 (A > G) and IL9 rs2069885 (G > A) single nucleotide polymorphisms was performed using the Real-Time PCR method based on LightSNiP kits assays. The present study demonstrated significant relationships between IL5 rs2069812 and IL9 rs2069885 polymorphisms and response to anti-TNF therapy. Presence of the IL5 rs2069812 A allele in patients positively correlated with better response to treatment (p = 0.022). With regard to IL9 rs2069885, patients carrying the A allele displayed better outcomes in anti-TNF therapy (p = 0.046). In addition, IL5 rs2069812 A and IL9 rs2069885 A alleles were associated with lower CRP and VAS values. The obtained results may indicate a significant role for IL-5 and IL-9 in the course of AS and response to anti-TNF therapy.

VDR Polymorphic Variants Are Related to Improvements in CRP and Disease Activity in Patients with Axial Spondyloarthritis That Undergo Anti-TNF Treatment.

Vitamin D deficiency is related with susceptibility or progression of various autoimmune diseases. The aim of the study was to assess potential relations between single nucleotide polymorphisms (SNPs) in the vitamin D receptor-coding gene (VDR): rs1544410 (BsmI), rs2228570 (FokI), rs731236 (TaqI), rs7975232 (ApaI), and disease activity in patients with axial spondyloarthritis (axSpA) undergoing anti-TNF therapy. The VDR rs731236 CT genotype was statistically more common among female patients (p = 0.027). An improvement of CRP equal to or higher than 50% after 3 months of anti-TNF therapy was observed for rs2228570 T allele (p = 0.002). After 6 months, CRP improvement equal to or higher than 75% was related to presence of the rs1544410 AA genotype (p = 0.027) and the rs731236 CC homozygotes (p = 0.047). Baseline BASDAI values were lower in individuals with the rs2228570 TT genotype (p = 0.036) and rs7975232 C allele (p = 0.029). After 6 months of treatment, lower BASDAI values were observed in AC heterozygotes (p = 0.005). The same AC genotype was more frequently detected in patients with remission (BASDAI ≤ 2) (p = 0.001) and in those achieving BASDAI improvement equal to or higher than 75% (p = 0.006). In conclusion, VDR SNPs were found to relate to CRP and BASDAI values at different time points of anti-TNF therapy.

Polymorphisms in the Genes Coding for TLRs, NLRs and RLRs Are Associated with Clinical Parameters of Patients with Acute Myeloid Leukemia.

Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) are major elements of the innate immune system that recognize pathogen-associated molecular patterns. Single-nucleotide polymorphisms (SNPs) in the TLR, NLR, and RLR genes may lead to an imbalance in the production of pro- and anti-inflammatory cytokines, changes in susceptibility to infections, the development of diseases, and carcinogenesis. Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by uncontrolled proliferation of transformed myeloid precursors. We retrospectively analyzed 90 AML patients. We investigated the effect of fifteen SNPs located in the genes coding for RLR1 (rs9695310, rs10738889, rs10813831), NOD1 (rs2075820, rs6958571), NOD2 (rs2066845, rs2066847, rs2066844), TLR3 (rs5743305, rs3775296, 3775291), TLR4 (rs4986791, rs4986790), and TLR9 (rs187084, rs5743836). We observed that TLR4 rs4986791, TLR9 rs5743836, and NOD2 rs2066847 were associated with CRP levels, while RLR-1 rs10738889 was associated with LDH level. Furthermore, we found TLR3 rs5743305 AA to be more common in patients with infections. We also found TLR9 rs187084 C to be associated with more favorable risk, and RLR-1 rs9695310 GG with higher age at diagnosis. In conclusion, the current study showed that SNPs in the genes encoding TLRs, NLRs, and RLRs may be potential biomarkers in patients with AML.

Soluble CD147 (BSG) as a Prognostic Marker in Multiple Myeloma.

CD147 (basigin, BSG) is a membrane-bound glycoprotein involved in energy metabolism that plays a role in cancer cell survival. Its soluble form is a promising marker of some diseases, but it is otherwise poorly studied. CD147 is overexpressed in multiple myeloma (MM) and is known to affect MM progression, while its genetic variants are associated with MM survival. In the present study, we aimed to assess serum soluble CD147 (sCD147) expression as a potential marker in MM. We found that sCD147 level was higher in MM patients compared to healthy individuals. It was also higher in patients with more advanced disease (ISS III) compared to both patients with less advanced MM and healthy individuals, while its level was observed to drop after positive response to treatment. Patients with high sCD147 were characterized by worse progression-free survival. sCD147 level did not directly correlate with bone marrow CD147 mRNA expression. In conclusion, this study suggests that serum sCD147 may be a prognostic marker in MM.

Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer.

The molecular mechanisms of telomerase reverse transcriptase (TERT) upregulation in breast cancer (BC) are complex. We compared genetic variability within TERT and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the TERT, MYC, TP53 and SP1 genes in BC patients and in BC organoids (3D cell cultures obtained from breast cancer tissues). We observed the same correlation in the blood of BC patients and in BC organoids between the expression of TERT and TP53. Only in BC patients was a correlation found between the expression of the TERT and MYC genes and between TP53 and MYC. We found associations between TERT genotypes (rs2735940 and rs10069690) and TP53 expression and telomere length. BC patients with the TT genotype rs2735940 have a shorter telomere length, but patients with A allele rs10069690 have a longer telomere length. BC patients with a short allele VNTR-MNS16A showed higher expression of the SP1 and had a longer telomere. Our results bring new insight into the regulation of TERT, MYC, TP53 and SP1 gene expression related to TERT genetic variability and telomere length. Our study also showed for the first time a similar relationship in the expression of the above genes in BC patients and in BC organoids. These findings suggest that TERT genetic variability, expression and telomere length might be useful biomarkers for BC, but their prognostic value may vary depending on the clinical parameters of BC patients and tumor aggressiveness.

Searching for New Genetic Biomarkers of Axial Spondyloarthritis.

Background: Axial spondyloarthritis (axSpA) is a chronic inflammatory condition of the spine. In addition to musculoskeletal symptoms, there are also extra-articular manifestations. The aim of this study was to search for new biomarkers associated with the clinical presentation and treatment response in axSpA patients. Methods: In this study, 106 axSpA patients and 110 healthy controls were enrolled. Six single-nucleotide polymorphisms (SNPs) were selected for genotyping: ERAP1 rs2287987, ERAP2 rs2549782, TNF rs1800629, TNFRSF1A rs767455, TNFRSF1B rs1061622, and FCGR2A rs1801274. Participants were examined at baseline and after 12 and 24 weeks of anti-TNF therapy. Results: SNPs associated with high axSpA initial activity were TNFRSF1A rs767455 and TNFRSF1B rs1061622 (p < 0.008). The ERAP1 rs2287987 AA genotype was more frequently observed in patients with enthesitis (AA vs. G+, p = 0.049), while the TNFRSF1B rs1061622 GG genotype was more common in participants with uveitis (GG vs. TT, p = 0.042). Potential in predicting anti-TNF treatment response was demonstrated by ERAP1 rs2287987, ERAP2 rs2549782, TNFRSF1B rs1061622, and FCGR2A rs1801274. Conclusions: SNPs can be used to identify patients at risk of severe disease to initiate treatment earlier. Genetic testing will allow clinicians to choose the right drug for the patient.

Case Report: Liver as a Source of Hematopoietic Stem Cells After Liver Transplantation Following Hematopoietic Stem Cell Transplantation.

We report a child with Fanconi anemia who, after hematopoietic stem cell transplantation (HSCT) complicated by acute graft-versus-host disease (GVHD), underwent orthotopic liver transplantation (OLT). Approximately 1 month after OLT, the presence of third-party genetic material from the liver donor was noted and in the next few weeks, the chimerism assessment revealed 100% liver donor leukocytes in the peripheral blood. The rapidly progressing GVHD with gut involvement resulted in patient's death 6 months after OLT. The liver can act as a clinically significant source of hematopoietic stem cells, and the liver donor's young age must be emphasized as potentially predisposing to this phenomenon. Transfer of OLT hematopoietic stem cells may not have clinical significance unless the patient is not immunocompetent or develops liver-transplantation associated GVHD, that can result in lymphocyte mediated elimination of original hematopoiesis. Patients with preexisting immunity disorder (such as primary or secondary immunodeficiency) might require intensified immunosuppressive therapy in peritransplant period as a prevention of liver-transplantation associated GVHD. Close monitoring of hematopoietic chimerism after OLT is warranted in patients at risk, because cytopenia or OLT hematopoiesis can reflect subclinical GVHD and further studies are necessary to elucidate this phenomenon.