Double-Negative T (DNT) Cells in Patients with Systemic Lupus Erythematosus.

Double-negative T (DNT) cells are a rare and unconventional T-lymphocyte subpopulation lacking both CD4 and CD8 markers. Their immunopathological roles and clinical relevance have yet to be elucidated. Beyond autoimmune lymphoproliferative syndrome (ALPS), these cells may also play a role in rheumatic disorders, including systemic lupus erythematosus (SLE); indeed, these two diseases share several autoimmune manifestations (including nephritis). Moreover, one of the main experimental murine models used to investigate lupus, namely the MRL/lpr mouse, is characterized by an expansion of DNT cells, which can support the production of pathogenic autoantibodies and/or modulate the immune response in this context. However, lupus murine models are not completely consistent with their human SLE counterpart, of course. In this mini review, we summarize and analyze the most relevant clinical studies investigating the DNT cell population in SLE patients. Overall, based on the present literature review and analysis, DNT cell homeostasis seems to be altered in patients with SLE. Indeed, most of the available clinical studies (which include both adults and children) reported an increased DNT cell percentage in SLE patients, especially during the active phases, even though no clear correlation with disease activity and/or inflammatory parameters has been clearly established. Well-designed, standardized, and longitudinal clinical studies focused on DNT cell population are needed, in order to further elucidate the actual contribution of these cells in SLE pathogenesis and their interactions with other immune cells (also implicated and/or altered in SLE, such as basophils), and clarify whether their expansion and/or immunophenotypic aspects may have any immunopathological relevance (and, then, represent potential disease markers and, in perspective, even therapeutic targets) or are just an unspecific epiphenomenon of autoimmunity.

Epidemiology of pediatric hematological malignancies in Kazakhstan: Data from Unified National Electronic Healthcare System 2014-2021.

We aimed to describe incidence and all-cause mortality of hematological pediatric malignancies (leukemia and lymphomas) in Kazakhstan based on nationwide large-scale healthcare data from the Unified National Electronic Healthcare System (UNEHS) for the 2014-2021 year period. The cohort included data of patients less than 18 years old with the diagnosis of hematological malignancies registered in the UNEHS (inpatient and outpatient registries) for the year period 2014-2021. Descriptive statistics were conducted to indicate socio-demographic characteristics of the cohort. Incidence and all-cause mortality were calculated per 100,000 population. Cox proportional hazard regression analysis was performed to investigate the association between determinants with the all-cause mortality. The total cohort consisted of 3357 children with leukemia and 1474 children with lymphomas. The mean age at diagnosis of leukemia and lymphomas was 7.3 ± 4.7 and 9.9 ± 4.9 years, respectively. The incidence rate of hematological malignancies was 6.8 per 100,000 in 2021. Patients with ALL had a higher incidence rate than patients with AML (3.4 and 1.2 per 100,000 in 2021, respectively). The incidence rate of HL and NHL was relatively similar which varied from 0.6 to 2.6 per 100,000 in 2014-2021. All-cause mortality of pediatric hematological malignancies varied from 1.1 to 1.5 per 100,000 in 2014-2021, with the peak in 2016 (1.7 per 100,000). Younger age is significantly associated with increased risk of all-cause mortality in children with AML. CONCUSION: Patients with ALL had a higher incidence rate than patients with AML. The incidence rate of HL and NHL was relatively similar. All-cause mortality rates for leukemia and lymphomas were quite stable during the study period. Younger age is significantly associated with increased all-cause mortality among AML patients. However, there is no significant association of age with all-cause mortality among ALL, HL and NHL. In order to obtain more reliable data and analysis on pediatric (hematological) malignancies, specific registries for childhood tumors (including detailed information on relapses, treatments, short and long-term side effects, and specific death causes) should be implemented. WHAT IS KNOWN: • Leukemias and lymphomas together account for around 45% of all pediatric malignancies. • Lymphoma accounts for 12% of all childhood malignancies; non-Hodgkin's lymphomas (NHL) are more frequent than Hodgkin's lymphomas (HL). WHAT IS NEW: • The incidence rate of ALL was higher than the incidence rate of AML throughout the whole study period, whereas all-cause mortality of ALL and AML was quite stable. • According to Cox PH analysis, younger age (0-5 years old) was associated with a higher risk of death among AML children compared to older children, and no significant association of age was observed with all-cause mortality among ALL and lymphomas.

Total serum IgA levels and HLA-DQB1*02:01 allelic status.

Immunoglobulin A Deficiency (IgAD) is the most common primary immunodeficiency and is significantly associated with Celiac Disease (CD), which recognizes a specific background of human leukocyte antigens (HLA) predisposition (including HLA-DQB1*02:01 allele). A number of studies investigated the role of HLA in IgAD etiopathogenesis: HLA-DQB1*02 alleles are included in the main haplotypes linked to this primary immunodeficiency. In this preliminary study, we investigated the potential impact of HLA-DQB1*02:01 allelic status on total serum IgA levels: 108 serum samples from the bone marrow donors' registry were analyzed for total IgA concentration with respect to the HLA-DQB1*02:01 status. Although total serum IgA levels between HLA-DQB1*02:01 carriers and HLA-DQB1*02:01 negative donors were not different, we observed a statistically significant difference (p=0.0118) in total serum IgA levels among donors with low IgA concentration (<80mg/dL) in the sub-analysis between HLA-DQB1*02:01 positive group (including both homozygous and heterozygous carriers) compared to HLA-DQB1*02:01 negative donors. Our results might suggest a role of HLA-DQB1*02:01 allelic variant in the determination of total serum IgA levels, at least in patients affected with IgA deficiency and/or otherwise predisposed to it; however, larger and more standardized studies are needed to confirm this speculation.

Natural Killer T (NKT) Cells in Autoimmune Hepatitis: Current Evidence from Basic and Clinical Research.

Natural killer T (NKT) cells are unconventional T cells that are activated by glycolipid antigens. They can produce a variety of inflammatory and regulatory cytokines and, therefore, modulate multiple aspects of the immune response in different pathological settings, including autoimmunity. NKT cells have also been implicated in the immunopathogenesis of autoimmune hepatitis, and in this review we summarize and analyze the main studies investigating the involvement and/or homeostasis of NKT cells in this disease. In detail, the evidence from both basic and clinical research has been specifically analyzed. Even though the experimental murine models supported a relevant role of NKT cells in immune-mediated hepatic injury, very few studies specifically investigated NKT cell homeostasis in patients with autoimmune hepatitis; however, these initial studies reported some alterations of NKT cells in these patients, which may also correlate with the disease activity to some extent. Further clinical studies are needed to investigate the potential role and use of NKT cell analysis as a disease marker of clinical relevance, and to better understand the precise cellular and molecular mechanisms by which NKT cells contribute to the pathogenesis of autoimmune hepatitis.

Celiac Disease in Uzbek Children: Insights into Disease Prevalence and Clinical Characteristics in Symptomatic Pediatric Patients.

BACKGROUND: A few studies on pediatric Celiac Disease (CD) are available from Central Asia. Recent immunogenetic research has highlighted that the HLA-DQ2/8 genetic predisposition to CD as well as the dietary intake of gluten in this geographical area, are comparable to other regions of the world where CD prevalence is known to be 1% or higher. METHODS: This is a prospective and cross-sectional study investigating the prevalence and clinical characteristics of CD in symptomatic children referred to the pediatric gastroenterology department of a tertiary hospital in Uzbekistan from 1 September 2021, until 31 July 2022. In addition to collecting the relevant information related to clinical manifestations and laboratory analyses from the clinical files, a specific survey was also administered to patients' guardians. Serological, histopathological, and immunogenetic parameters specific to CD, fecal zonulin, and pancreatic elastases were assessed in CD patients. RESULTS: The study population consisted of 206 children. Overall, almost all of them (n = 192; 93.2%) were referred because of gastrointestinal manifestations, which were associated with extra-gastrointestinal manifestations in most cases (n = 153; 74.3%); a minority (n = 14; 6.8%) was mainly referred due short stature and/or growth failure only. Among all of these study participants, CD was diagnosed in 11 children (5.3%). Notably, although diarrhea was similarly reported in CD and non-CD patients, watery diarrhea (type 7 according to the Bristol stool scale) was much more frequently and significantly observed in the former group. All of these CD patients showed anti-tTG IgA 10 times higher than the upper normal limit, except one child with lower serum levels of total IgA; however, all of them received a diagnostic confirmation by histopathological analysis due to the lack of EMA testing in the country. Notably, most CD children (82%) showed a Marsh III histological grading. Around half patients (54.5%) showed zonulin values above the reference range, whereas none showed insufficient levels of pancreatic elastase. However, no correlation or association between zonulin and clinical, laboratory, histopathological, and immunogenetic parameters was found. CONCLUSIONS: This study may further suggest a relevant prevalence of CD in Uzbek children, based on this partial picture emerging from symptomatic patients only. Additionally, we highlighted the prevalence of typical CD forms with watery diarrhea, which should strongly support a full diagnostic work-up for CD in the local clinical setting. The high levels of anti-tTG IgA and high Marsh grade might also lead us to speculate a significant diagnostic delay despite the classical clinical expression of CD.

Pediatric erythema ab igne: clinical aspects and diagnostic issues.

Erythema ab igne is a dermatological condition resulting from repeated low-grade heat exposure (below the burning point), which can variably manifest with reticulated erythema and skin hyperpigmentation. Not infrequently, the cause of such a skin disorder is not immediately evident or reported by patients, especially if these are children. Compared to adults, erythema ab igne is rare in children and, if the general practitioners and pediatricians are not aware of this disorder, pediatric patients are often addressed to rheumatologists and/or undergo useless immunological investigations. Here, we performed a systematic case-based review, which finally included 32 cases of pediatric erythema ab igne (in addition to our new clinical report), and discussed the main clinical aspects and issues of this clinical entity in children. In detail, similarities of erythema ab igne with livedo reticularis and/or vasculitis-related rashes sometimes can lead to perform a panel of immunological investigations, which could be avoided. Indeed, our analysis emphasizes the importance of a careful and complete patient's anamnesis, including active questioning about the potential exposure to any physical agents (including heat sources) that may cause dermatological lesions. We also highlight some peculiarities in terms of location and heat injury in children developing erythema ab igne, based on the presence or absence of comorbidities. CONCLUSION: The occurrence of erythema ab igne in children (and especially in adolescents) is likely to increase in the next years because of the greater and sometimes inappropriate use of technological devices. Physicians should be aware of this condition in order to prevent patients from useless investigations, especially in the differential diagnosis of rheumatic disorders. A careful and complete patient's history with active questioning about the potential exposure to heating source is often decisive to diagnose erythema ab igne. WHAT IS KNOWN: • Erythema ab igne is a dermatological condition which is mainly described in adults exposed to heating source at the workplace. WHAT IS NEW: • The occurrence of erythema ab igne in children is likely to increase in the next years because of the greater and sometimes inappropriate use of technological devices. • Erythema ab igne in children can be classified in two main categories, based on the presence or absence of comorbidity. • A careful and complete anamnesis (including the active questioning about potential exposure to any heating source) is the mainstay for diagnosing erythema ab igne in children.

Serum immunoglobulin A (IgA) levels in children affected with Juvenile Idiopathic Arthritis.

Background and objective: Immunoglobulin A (IgA) is the most abundant antibody isotype in the human body, considering its presence on the mucosal surfaces, in addition to the amount circulating in the bloodstream. Serum IgA levels can be variably altered in several pathological settings. However, very few studies specifically investigated serum IgA in Juvenile Idiopathic Arthritis (JIA). In the present study, we specifically assessed serum IgA levels in our cohort of patients affected with JIA. Methods: In this cross-sectional study, serum IgA levels were measured in patients with JIA (and age-matched controls) and analyzed according to age class. The correlation of serum IgA levels with hematological, inflammatory, and disease activity parameters was assessed. Results: No significant difference in the frequency of low IgA levels (according to the definition of complete and partial IgA deficiency) was observed between JIA patients and controls, overall. This pediatric study population showed a progressive increase of total serum IgA concentrations with age, as expected; however, in JIA patients aged 10-17 years, total IgA serum levels resulted to be significantly higher than in age-matched control subjects. No clear correlation between IgA levels and the examined inflammatory, hematological, and disease activity parameters was observed in JIA patients, except for the erythrocyte sedimentation rate (ESR) in oligoarticular JIA patients: here, serum IgA levels showed a positive and moderate covariation with ESR, which was also observed for disease activity (JADAS-10) in selected oJIA patients without biological therapy. Conclusions: In our cohort of JIA patients, total serum IgA levels were not reduced and were actually increased in adolescents compared to controls. Larger studies are needed to confirm this finding, which cannot be certainly explained based on the available data in this study, even though JIA disease control and/or chronic inflammation may be implicated to some extent.

Pediatric Extra-Renal Nephroblastoma (Wilms' Tumor): A Systematic Case-Based Review.

Wilms Tumor (WT) is one of the most common renal tumors in the pediatric population. Occasionally, WT can primarily develop outside the kidneys (Extra-Renal Wilms Tumor, ERWT). Most pediatric ERWTs develop in the abdominal cavity and pelvis, whereas the occurrence of this tumor in other extra-renal sites represents a minor part of ERWT cases. In addition to describing a case of spinal ERWT (associated with spinal dysraphism) in a 4-year boy (to add a further clinical experience on this very rare pediatric tumor), we performed a case-based systematic literature review on pediatric ERWT. We retrieved 72 papers providing enough information on the diagnosis, treatment, and outcomes of 98 ERWT pediatric patients. Our research highlighted that a multimodal approach involving both chemotherapy and radiotherapy, after partial or complete tumor resection in most cases, was typically used, but there is no standardized therapeutic approach for this pediatric malignancy. However, this tumor may be potentially treated with a better success rate if the diagnostic confirmation is not delayed, the mass can be totally resected, and an appropriate and, possibly, tailored multimodal treatment can be promptly established. In this regard, an international agreement on a unique staging system for (pediatric) ERWT is definitely needed, as well as the development of international research, which may be able to gather several children diagnosed with ERWT and, possibly, lead to clinical trials which should also include developing countries.

Case report: Atypical teratoid/rhabdoid tumor of the lateral ventricle in a male adolescent (case-based review and diagnostic challenges in developing countries).

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly malignant central nervous system (CNS) embryonal neoplasm: it accounts for <2% of all pediatric CNS tumors and occurs mainly in infants and young children. The primary site of this tumor is usually the posterior cranial fossa. Supratentorial and, in detail, latero-ventricular location is extremely uncommon, especially in adolescents. This tumor is characterized by rapid growth and spread in cerebrospinal fluid and, therefore, it is characterized by a poor prognosis. Neurological signs and symptoms are related the location of the tumor. The radiological features of AT/RT are nonspecific. Immunohistochemical staining for loss of nuclear integrase interactor 1 (INI1) expression is considered a reliable criterion for the diagnosis of this type of tumor. AT/RT has been linked to mutations of SMARCB1 or, rarely, SMARCA4 genes, which function as tumor suppressor genes. Currently, there is no validated protocol of treatment for children with AT/RT, and multimodality treatment (consisting of surgery, chemotherapy, and radiation therapy) is considered. In this case report, we describe a 15-year-old adolescent with an AT/RT of the left lateral ventricle. Despite the late diagnosis, the multimodal therapeutic approach provided a good outcome for our patient at 21 months' follow-up. Based on our case-based review, early diagnosis and a multimodal approach to treatment play a key role in improving the survival of patients with this diagnosis. Implementing a system supporting pathological and molecular analyses for developing countries and, in general, for non-academic centers is of primary importance to timely diagnose and treat rare tumors, such as AT/RT.

Central and effector memory T cells in peripheral blood of patients with interstitial pneumonia: preliminary clues from a COVID-19 study.

BACKGROUND: SARS-CoV-2 pre-existing T-cell immune reactivity can be present in some people. A general perturbation of the main peripheral lymphocyte subsets has been described in severe COVID-19 patients, but very few studies assessed the general memory T-cell homeostasis in the acute phase of COVID-19. Here, we performed a general analysis of the main memory T cell populations in the peripheral blood of patients admitted to the hospital for a confirmed or probable COVID-19 diagnosis. METHODS: In this cross-sectional study, adult patients (aged ≥ 18 years) needing hospital admission for respiratory disease due to confirmed or probable COVID-19, were recruited before starting the therapeutic protocol for this disease. In addition to the assessment of the general lymphocyte subpopulations in the early phase of COVID-19, central memory T cells (Tmcentr cells: CD45RO+CCR7+) and effector memory T cells (Tmeff cells: CD45RO+CCR7-) were assessed by multi-color flow cytometry, in comparison to a control group. RESULTS: During the study period, 148 study participants were recruited. Among them, 58 patients turned out positive for SARS-CoV-2 PCR (including both patients with interstitial pneumonia [PCR+Pn+] and without this complication [PCR+Pn-]), whereas the remaining 90 patients resulted to be SARS-CoV-2 PCR negative, even though all were affected with interstitial pneumonia [PCR-Pn+]. Additionally, 28 control patients without any ongoing respiratory disease were recruited. A clear unbalance in the T memory compartment emerged from this analysis on the whole pool of T cells (CD3+ cells), showing a significant increase in Tmcentr cells and, conversely, a significant decrease in Tmeff cells in both pneumonia groups (PCR+Pn+ and PCR-Pn+) compared to the controls; PCR+Pn- group showed trends comprised between patients with pneumonia (from one side) and the control group (from the other side). This perturbation inside the memory T cell compartment was also observed in the individual analysis of the four main T cell subpopulations, based upon the differential expression of CD4 and/or CD8 markers. CONCLUSION: Overall, we observed both absolute and relative increases of Tmcentr cells and decrease of Tmeff cells in patients affected with interstitial pneumonia (regardless of the positive or negative results of SARS-CoV-2 PCR), compared to controls. These results need confirmation from additional research, in order to consider this finding as a potential biological marker of interstitial lung involvement in patients affected with viral respiratory infections.

Celiac Disease and Gallbladder: Pathophysiological Aspects and Clinical Issues.

Background: Celiac Disease (CD) is an immune-mediated disorder which primarily affects the small intestine; however, extra-intestinal organs are often affected by the pathological process, too. As regards the digestive system, liver alterations in CD patients have been widely described, which can also extend to the biliary tract. Notably, gallbladder function can be altered in CD patients. In this review, we specifically analyze and summarize the main pathophysiological aspects and clinical evidence of gallbladder dysfunction in CD patients, in order to discuss the potential medical complications and clinical research gaps. In addition to some perturbations of bile composition, CD patients can develop gallbladder dysmotility, which mainly expresses with an impaired emptying during the digestive phase. The main pathophysiological determinant is a perturbation of cholecystokinin secretion by the specific duodenal enteroendocrine cells in response to the appropriate nutrient stimulation in CD patients. This situation appears to be reversible with a gluten-free diet in most cases. Despite this gallbladder impairment, CD patients do not seem to be more predisposed to gallbladder complications, such as calculous and acalculous cholecystitis. However, very few clinical studies have actively investigated these clinical aspects, which may not be completely evidenced so far; alternatively, the substantial improvements in the last two decades regarding CD diagnosis, which have reduced the diagnostic delay (and related dietary treatment), may have lessened the potential clinical consequences of CD-related gallbladder dysfunction. Specific clinical studies focused on these aspects are needed for a better understanding of the clinical implications of gallbladder alterations in CD patients.

Analysis of Peripheral Blood Basophils in Pediatric Systemic Lupus Erythematosus.

Basophils are the least abundant circulating leukocytes, and their immunological role has not yet been completely elucidated. There is evidence supporting their immunomodulatory role in several pathological settings; recently, studies in both experimental models and humans suggested that basophil homeostasis may be altered in systemic lupus erythematosus (SLE). Here, we first assessed circulating basophils in children affected with pediatric SLE (pSLE). In this cross-sectional study, circulating basophils were enumerated by fluorescence-based flow cytometry analysis in children affected with pSLE, in addition to children suffering from juvenile idiopathic arthritis (JIA) or non-inflammatory/non-rheumatic conditions. This study included 52 pediatric patients distributed in these three groups. We observed a statistically significant reduction of peripherally circulating basophils in children with pSLE compared to the other two groups of patients. This preliminary study is consistent with the available studies in adult patients with SLE showing a reduced number of circulating basophils. However, further research is needed to draw final conclusions on basophils' homeostasis in pSLE, in addition to their correlation with the disease activity and concomitant therapies.

Mycoplasma pneumoniae Infections and Primary Immune Deficiencies.

Mycoplasma pneumoniae (M. pneumoniae) is one of the leading causes of community-acquired pneumonia in children and is also implicated in a variety of reactive extrapulmonary diseases. Recurrent and/or severe respiratory infections are one of the most frequent manifestations of several types of primary immunodeficiency. Here, we reviewed the medical literature to assess the potential relevance of M. pneumoniae in the infections observed in children affected with combined, humoral, and innate primary immune deficiencies. M. pneumoniae does not result to be epidemiologically prevalent as a cause of pneumonia in children affected by primary immunodeficiencies, but this infection can have a persistent or severe course in this category of patients. Indeed, the active search of M. pneumoniae could be useful and appropriate especially in children with humoral immune deficiencies. Indeed, most cases of M. pneumoniae infection in primary immunodeficiencies are described in patients affected by a/hypo-gammaglobulinemia.

Anti-Inflammatory, Antioxidant, and Anti-Atherosclerotic Effects of Natural Supplements on Patients with FMF-Related AA Amyloidosis: A Non-Randomized 24-Week Open-Label Interventional Study.

We aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction, and oxidative stress in a cohort of familial Mediterranean fever (FMF) patients with Serum Amyloid A amyloidosis, in a non-randomized, 24-week open-label interventional study. Morinda citrifolia (anti-atherosclerotic-AAL), omega-3 (anti-inflammatory-AIC), and extract with Alaskan blueberry (antioxidant-AOL) were given to patients with FMF-related biopsy-proven AA amyloidosis. Patients were >18 years and had proteinuria (>3500 mg/day) but a normal estimated glomerular filtration rate (eGFR). Arterial flow-mediated dilatation (FMD), carotid intima media thickness (CIMT), and serum biomarkers asymmetric dimethylarginine (ADMA), high sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and glutathione peroxidase (GSH-Px) were studied at baseline and after 24 weeks of treatment. A total of 67 FMF-related amyloidosis patients (52 male (77.6%); median age 36 years (range 21−66)) were enrolled. At the end of a 24-week treatment period with AAL, AIC, and AOL combination therapy, ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px, and FMD levels were significantly increased. Changes in inflammatory markers PTX3, and hsCRP were negatively correlated with FMD change, and positively correlated with decreases in proteinuria, ADMA, MDA, cholesterol, and CIMT. Treatment with AAL, AIC and AOL combination for 24 weeks were significantly associated with reduction in inflammatory markers, improved endothelial functions, and oxidative state. Efficient control of these three mechanisms can have long term cardiovascular and renal benefits for patients with AA amyloidosis.

Assessment of Surrogate Markers for Cardiovascular Disease in Familial Mediterranean Fever-Related Amyloidosis Patients Homozygous for M694V Mutation in MEFV Gene.

Cardiovascular disease (CVD) remains underestimated in familial Mediterranean fever-associated AA amyloidosis (FMF-AA). We aimed to compare early markers of endothelial dysfunction and atherosclerosis in FMF-AA with a homozygous M694V mutation (Group 1 = 76 patients) in the Mediterranean fever (MEFV) gene and in patients with other genotypes (Group 2 = 93 patients). Measures of increased risk for future CVD events and endothelial dysfunction, including flow-mediated dilatation (FMD), pentraxin-3 (PTX3), and carotid intima-media thickness (cIMT), and fibroblast growth factor 23 (FGF23) as a marker of atherosclerotic vascular disease were compared between groups. The frequency of clinical FMF manifestations did not differ between the two groups apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p < 0.05). FMD was significantly lower in Group 1 when compared with Group 2 (MD [95% CI]: −0.6 [(−0.89)−(−0.31)]). cIMT, FGF23, and PTX3 levels were higher in Group 1 (cIMT MD [95% CI]: 0.12 [0.08−0.16]; FGF23 MD [95% CI]: 12.8 [5.9−19.6]; PTX3 MD [95% CI]: 13.3 [8.9−17.5]). In patients with FMF-AA, M694V homozygosity is associated with lower FMD values and higher cIMT, FGF23, and PTX3 levels, suggesting increased CVD risk profiles. These data suggest that a genotype−phenotype association exists in terms of endothelial dysfunction and atherosclerosis in patients with FMF-AA.

Association Study of Anticitrullinated Peptide Antibody Status with Clinical Manifestations and SNPs in Patients Affected with Rheumatoid Arthritis: A Pilot Study.

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that leads to disability due to articular and extra-articular damage. RA prevalence is variable. The disease is most common among females with a 3 : 1 ratio. The interaction of environmental and host factors contributes to RA development. Currently, the genome-wide association studies (GWAS) give the opportunity to uncover the RA genetic background. Anticitrullinated peptide antibody (ACPA) is a highly specific RA antibody, associated with poor prognosis and severe course of RA, and regulated by numerous genes. Our study is aimed at investigating whether there are any clinical and genetic aspects correlate with ACPA presence in Kazakhstani patients with RA. Indeed, the available studies on this subject are focused on Caucasian and East Asian populations (mainly Japanese and Chinese), and there are scarce data from Central Asia. Methods: Our study included 70 RA patients. Patients' blood samples were collected and genotyped for 14 SNPs by real-time polymerase chain reaction (RT-PCR). General examination, anamnestic, and clinical and laboratory data collection were carried out. Statistical analysis was performed using R statistics. Results and Conclusion. Our study revealed a significant association of ACPA positivity with Fc receptor-like 3 (FCRL3) and ACPA negativity with signal transducer and activator of transcription 4 (STAT4) genes, but not with T cell activation Rho GTPase activating protein (TAGAP). In addition, ACPA positivity was associated with radiographic progression, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), age of RA onset, the patient global assessment, body mass index (BMI), and Gamma globulin. Conclusion: Remained 11 earlier identified significantly associated in Caucasian and Asian population SNPs were not replicated in our cohort. Further studies on larger cohorts are needed to confirm our findings with higher confidence levels and stronger statistical power.

Comparison between SARS-CoV-2 positive and negative pneumonia in children: A retrospective analysis at the beginning of the pandemic.

BACKGROUND: Even though coronavirus 2019 disease (COVID-19) clinical course in children is much milder than in adults, pneumonia can occur in the pediatric population as well. Here, we reported a single-center pediatric case series of COVID-19 from Kazakhstan during the first wave of pandemic. AIM: To analyze the main clinical and laboratory aspects in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive and negative children diagnosed with pneumonia. METHODS: This is a retrospective analysis of 54 children, who were medically assessed as close contacts of COVID-19 adults in their family setting, between June and September 2020. These children were all hospitalized: We compared the clinical and laboratory characteristics of children affected with pneumonia in the presence (group 1) or absence (group 2) of SARS-CoV-2 infection. RESULTS: Overall, the main clinical manifestations at the admission were fever, cough, loss of appetite, fatigue/weakness, nasal congestion and/or rhinorrhea, and dyspnea. Based on the SARS-CoV-2 polymerase chain reaction (PCR) test, 24 positive children with pneumonia (group 1) and 20 negative children with pneumonia (group 2) were identified; 10 positive children did not show any radiological findings of pneumonia. No significant differences were found between the two pneumonia study groups for any clinical and laboratory parameters, except for C-reactive protein (CRP). Of course, both pneumonia groups showed increased CRP values; however, the COVID-19 pneumonia group 1 showed a significantly higher increase of CRP compared to group 2. CONCLUSION: In our case series of children assessed for SARS-CoV-2 infection based on contact tracing, the acute inflammatory response and, in detail, CRP increase resulted to be more pronounced in COVID-19 children with pneumonia than in children with SARS-CoV-2-unrelated pneumonia. However, because of multiple limitations of this study, larger, controlled and more complete clinical studies are needed to verify this finding.