Immunological Tests Research Articles

Immunological indicators of complications of surgical bowel disease in children

The article is devoted to the development of immunological indicators of intestinal inflammation in children, which is of great importance for health authorities when organizing specialized pediatric and surgical services. The proposed method contributes to the early diagnosis and prevention of complications of inflammatory surgical bowel diseases in children, which is of great practical importance. The purpose of the study: To develop immunological indicators of complications of surgical bowel diseases in children. A retrospective analysis of 867 case histories of children who received inpatient treatment at the Department of Pediatric Surgery of the Bukhara branch of the Republican Scientific Center of Emergency Medical Care from 2019 to 2022 for surgical diseases of the gastrointestinal tract was carried out. The authors conducted an immunological study of 91 pediatric patients. All children underwent immunological blood tests: cellular and humoral immunity, cytokines (TNFα, IFNα, IL-8, MCP-1 and vascular endothelial growth factor VEGF-A) were studied. For the prevention of postoperative complications of CKD in children, it is recommended to determine IFNα in the blood serum in the period before surgery to solve the indications for immunocorrection. A noticeable positive relationship was established between IFNα and CD8 – r = 0.34, between IFNα and CD23 – r = 0.38, between IFNα and IgA – r = 0.39, between IFNα and PCT – r = 0.36. At the same time, PCT has a noticeable negative relationship with CD16 – r = -0.31 and with CD8 – r = -0.31 against the background of a noticeable positive relationship with IgG – r = 0.32 and IFNα – r = 0.36. It was found that IFNα is a more informative indicator of the effectiveness of the immune response, and PCT is an indicator of the effectiveness of antibacterial therapy in surgical bowel diseases in children

Immunological Pathways in the Development of Postoperative Hyperamylasemia and Postoperative Pancreatitis – Preliminary Results

Postoperative pancreatitis complications can be separated into two main groups based on literature reviews and clinical and experimental trials. Some authors suggest that postoperative pancreatitis is a severe complication that should be treated conservatively and operatively if needed. Other authors defend an opposite opinion that only postoperative hyperamylasemia exists, which is a transitory condition with no risk of complications.
 At “Alexandrovska” University Hospital for Active Treatment, Clinic of General and Liver-Pancreatic Surgery, a cohort of patients with increased amylase concentrations in the postoperative period between January 2017 and December 2018 were studied and followed with immunological and biochemical tests for interleukin (IL)-6. Regardless of the type of surgery to which they were subjected, all patients who presented with an elevated amylase concentration in the postoperative period were selected. The working hypotheses were the following: i) IL-6 is directly relevant in the development of postoperative pancreatitis; ii) the concentration of IL-6 is a prognostic factor in the early postoperative period and marks the boundary at which patients will develop postoperative pancreatitis and its various clinical manifestations; and iii) the postoperative period is accompanied by transient postoperative hyperamylasemia and absence of complications. To test these hypotheses, the values of IL-6 were statistically analyzed using SPSS v23 software.
 The results show that, with a 95% confidence interval (CI), a statistically significant difference is found in the concentration of IL-6 in patients who developed postoperative pancreatitis versus those with transient hyperamylasemia.
 The present study shows a direct link between the immunological marker, IL-6, and the course of both postoperative pancreatitis and transient hyperamylasemia, making this marker valuable in elucidating the differences in the development of postoperative pancreatitis and transient hyperamylasemia in the early postoperative period. Thus, IL-6 can be used to reach the correct diagnosis and decide effective treatment.

Клінічний випадок маніфестації первинного імунодефіциту з лімфоми Беркіта

Lymphoma is a group of neoplastic diseases characterized by the clonal proliferation of lymphoid cells, manifested by the response of various stages of differentiation of normal B-lymphocytes, less often T-lymphocytes or natural killer cells. The etiology of most lymphomas is unknown. Some of the proven causal-consequence factors are: viral infections and immunodeficiency conditions. Purpose - to draw the attention of non-immunologists to the peculiarities of detecting the primary immunodeficiency (PID) states and the problem of their late diagnosis based on the data of a clinical case. Clinical case. A clinical observation of severe non-genetically differentiated PID is given. Screening signs of PID in the form of recurrent infectious respiratory tract syndrome and frequent long-term use of antibacterial drugs are highlighted, which should alert doctors to clinical and immunological markers of primary immunodeficiency. The presence of Burkitt's lymphoma in the boy also does not exclude the possibility of the manifestation of an immunodeficiency state, both secondary to the drug treatment of lymphoma, and primary, which can manifest itself in puberty. Common variable immunodeficiency is one of those PIDs that "starts" with Burkitt's lymphoma. Conclusions. The problem of low detection of probable PID in children in Ukraine is urgent. Primary care physicians are the first to be able to partially solve this problem by examining the infectious history and laboratory screening tests. There is incomplete awareness of related medical specialties regarding the signs of PID in lymphoproliferative syndrome in children. This clinical case demonstrates signs of PID at an early age. Low detection is also associated with poor capacity and quality and/or lack of immunological laboratory testing, particularly in public facilities. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the of the child’s parents was obtained for the research No conflict of interests was declared by the authors.

Invited Commentary: The Winding Road to Identifying the Annual Rate of Tuberculosis Infection.

Many persons with immunological tests indicating Mycobacterium tuberculosis infection, such as tuberculin skin tests or interferon-γ release assays, are at risk of progression to tuberculosis disease. Persons whose tests revert to negative may no longer be at such risk. Therefore, identifying the rate of test reversion, potentially indicating cure of M. tuberculosis infection, is an important area of investigation. In their accompanying article (Am J Epidemiol. 2023;192(12):1937-1943), Schwalb et al. extract data on test reversion from prechemotherapy literature and construct a model to predict the rate of reversion, and thus the likely cure of infection. Unfortunately, the incompleteness of the historical data and the use of imprecise definitions of test positivity and reversion lead to substantial misclassification and limit the usefulness of the model. Better definitions and improved tests will be needed in order to develop a clear picture of this aspect of the natural history of tuberculosis.

Treatment of spontaneous canine mast cell tumors by electrochemotherapy combined with IL-12 gene electrotransfer: Comparison of intratumoral and peritumoral application of IL-12

The combined treatment of electrochemotherapy (ECT) and interleukin-12 (IL-12) gene electrotransfer (GET) has already been used in clinical studies in dogs to treat various histological types of spontaneous tumors. The results of these studies show that the treatment is safe and effective. However, in these clinical studies, the routes of administration of IL-12 GET were either intratumoral (i.t.) or peritumoral (peri.t.). Therefore, the objective of this clinical trial was to compare the two IL-12 GET routes of administration in combination with ECT and their contribution to the enhanced ECT response. Seventy-seven dogs with spontaneous mast cell tumors (MCTs) were divided into three groups: one treated with a combination of ECT + GET peri. t. (29 dogs), the second with the combination of ECT + GET i.t. (30 dogs), and the third with ECT alone (18 dogs). In addition, immunohistochemical studies of tumor samples before treatment and flow cytometry of peripheral blood mononuclear cells (PBMCs) before and after treatment were performed to determine any immunological aspects of the treatment. The results showed that local tumor control was significantly better in the ECT + GET i.t. group (p < 0.050) than in the ECT + GET peri.t. or ECT groups. In addition, disease-free interval (DFI) and progression-free survival (PFS) were significantly longer in the ECT + GET i.t. group than in the other two groups (p < 0.050). The data on local tumor response, DFI, and PFS were consistent with immunological tests, as we detected an increased percentage of antitumor immune cells in the blood after treatment in the ECT + GET i.t. group, which also indicated the induction of a systemic immune response. In addition, we did not observe any unwanted severe or long-lasting side effects. Finally, due to the more pronounced local response after ECT + GET i.t., we suggest that treatment response assessment should be performed at least two months after treatment, which meets the iRECIST criteria.

P70 UNEXPLAINED TRANSIENT BIVENTRICULAR DYSFUNCTION IN A PATIENT WITH DISSEMINATED TUBERCULOSIS AND SEVERE EOSINOPHILIA

Abstract Introduction Tuberculosis (TB) is an infectious disease with significant global burden. Pericardial injury is relatively common, while myocardial involvement has only rarely been described. Case presentation A 29-years-old man from Gambia with disseminated TB, treated with isoniazid, rifampin, pyrazinamide and ethambutol, was admitted to our hospital. He denied history of heart disease, cardiovascular risk factors and voluptuary habits. Laboratory exams revealed severe eosinophilia without microbiological evidence of parasitic infection; a lymphocyte proliferation test ruled out allergic reaction to anti-TB therapy. Baseline echocardiographic evaluation showed normal cardiac function with negative troponin. The patient, subsequently, developed worsening dyspnoea and asthenia with progressive biventricular dysfunction. Therefore, he was admitted to our department for further investigations. Cardiac magnetic resonance (CMR) showed a 20% left ventricular ejection fraction and absence of myocardial oedema or fibrosis [Fig.1]. Coronary CT angiography (CCTA) was unremarkable. Endomyocardial biopsy (EMB) showed absence of TB lesions or eosinophilic infiltration. Cardiac troponin and electrocardiogram remained negative throughout. Optimal medical therapy (OMT) for heart failure was promptly initiated. After several months an almost complete recovery of cardiac function was documented [Fig.2]. Discussion In cases of ventricular dysfunction, establishing an etiological diagnosis is imperative, though sometimes challenging. When pre-test probability is low, CAD can be ruled out by CCTA. Myocarditis is a common cause of reversible cardiac dysfunction. In this case, the absence of Lake Louise criteria, negative bioptic findings, persistently negative cardiac troponin and microbiological tests argue against this diagnosis. However, the timing of investigations can affect diagnostic accuracy; furthermore, focal lesions can be missed by EMB, leading to false negative results. Alcoholic cardiomyopathy (CMP) could be an option, but it was not considered due to absence of alcohol consumption. The clinical picture was not compatible with a typical CMP phenotype. Immune-mediated reaction to anti-TB drugs was ruled out by immunological testing. Although not previously described, ethambutol and pyrazinamide direct cardiotoxicity may explain transient impairment of cardiac function. Recovery may be related to withdrawal of these drugs and introduction of guideline-directed OMT.

Monogenic inborn errors of immunity in autoimmune disorders.

To estimate the prevalence of monogenic inborn errors of immunity in patients with autoimmune diseases (AID), the study included 56 subjects (male:female ratio: 1.07) with mean age of onset of autoimmunity 7 years (4 months-46 years). 21/56 had polyautoimmunity. 5/56 patients met the JMF criteria for PID. The different AID referred were hematological (42%) > gastrointestinal (GI) (16%) > skin (14%) > endocrine (10%) > rheumatological (8%) > renal (6%) > neurological (2%). 36/56 reported recurrent infections. 27/56 were on polyimmunotherapy. 18/52 (35%) had CD19 lymphopenia, 24/52 (46%) had CD4 lymphopenia, 11/52 (21%) had CD8 lymphopenia, and 14/48 (29%) had NK lymphopenia. 21/50 (42%) had hypogammaglobinemia; 3 of whom were given rituximab. 28/56 were found to have pathogenic variants among PIRD genes. These 28 patients had 42 AID among which hematological was most common (50%) > GI (14%) =skin (14%)> endocrine (9%) >rheumatological (7%) > renal and neurological (2%). Hematological AID was the most common AID (75%) in children with PIRD. Positive predictive value (PPV) of abnormal immunological tests was 50% and sensitivity of 70%. JMF criteria had specificity of 100% in identifying PIRD and sensitivity of 17%. Polyautoimmunity had a PPV of 35% and sensitivity of 40%. 11/28 of these children were offered transplant. 8/28 were started on sirolimus, 2/28 on abatacept, and 3/28 on baricitinib/ruxolitinib after diagnosis. In conclusion, 50% of children with AID have underlying PIRD. LRBA deficiency and STAT1 GOF were the most common PIRD. Age at presentation, number of autoimmunity, routine immunological tests, and JMF criteria are not predictive of underlying PIRD. Early diagnosis with exome sequencing alters the prognosis and opens new therapeutic avenue.

Bilateral anterior thalamic symmetrical infarction: a case study

BackgroundBilateral anterior thalamic symmetrical infarction is very rarely observed in clinical practice and has rarely been reported in the literature. In this paper we introduce a patient with bilateral anterior thalamic symmetrical infarction and discuss his symptoms, treatment process, and follow-up visit results, as well as the potential pathological mechanisms of the disease.Case presentation: A 71-year-old male had a sudden cognitive decline four days prior to medical consultation. The patient’s brain MRI showed symmetrical high signals in the anterior part of both sides of the thalamus. The patient’s head MRV and immunological tests were normal, and we considered that this patient had a rare case of bilateral anterior thalamic infarction. After 10 days of anti-platelet aggregation that lowered blood lipids and improved circulation, the patient’s symptoms significantly abated. Two years later, we found through telephone follow-up that the patient’s symptoms had not relapsed substantially and that he was able to perform self-care, having only continued to suffer a slight decline in short-term memory.ConclusionFor patients with bilateral prethalamic lesions who have only acute cognitive impairment, if the lesions conform to the blood supply area of both thalamic nodular arteries and DWI shows a high signal, the diagnosis of acute cerebral infarction should be considered, and the standard treatment plan for cerebral infarction should be given as soon as possible.

Infertility - causes, diagnosis, preventive measures and methods of treatment

The problem of infertility affects approximately 20% of married couples, and the number of people affected by this problem is still increasing[5,6]. Developed countries are characterized by the prevalence of primary infertility, while in developing countries there is a high rate of secondary infertility[8,9]. The most common cause of marital infertility is obstruction of the fallopian tubes, which occurs in 30-35% of women and requires surgical intervention. However, both sexes are dominated by immunological and hormonal disorders (25%-30% of cases)[3,4]. The basic examination in which male fertility is determined is the semen analysis, while in women, many tests should be performed in order to make a diagnosis: anamnesis, gynecological examination, ultrasound performed repeatedly during the menstrual cycle (ovulation assessment), hormonal and immunological tests, post-coital tests, bacteriological cultures, hysterosalpingography or laparoscopy [20]. In vitro fertilization is the most effective of all methods of infertility treatment. In vitro fertilization can be performed using the classical method by adding prepared sperm to the egg cells or by microinjection of the sperm into the egg cell[21].

Monogenic inborn errors of immunity in autoimmune disorders

To estimate the prevalence of monogenic inborn errors of immunity in patients with autoimmune diseases. This was a retrospective and prospective cohort study. The study included 56 subjects (Male:Female ratio: 1.07) with mean age of onset of autoimmunity of 7 years (4months-46 years). 21/57 (37.5%) had polyautoimmunity. 5/56 patients met the JMF criteria for PID. The different AID referred were hematological (42%) > GI (16%) > Skin (14%) > Endocrine (10%) > Rheumatological (8%) > Renal (6%) > Neurological (2%). 36/57 (63%) reported recurrent infections. 27/56 were on polytherapy, 46 had received steroids. 18/52 (35%) had CD19 lymphopenia, 24/52(46%) had CD4 lymphopenia, 11/52(21%) had CD8 lymphopenia, 14/48 (29%) had NK lymphopenia. 20/50 (42%) had hypogammaglobinemia. 28/56 (50%) were found to have pathogenic variants among PIRD genes (LRBA:6, STAT1 GOF: 3, CTLA4: 2, ACP5: 2, 1 each with NFKB1, NLRP12, CARD11 GOF, STAT3 GOF, RTEL1, NCF2, ATM, RAG1, BTK, IL12RB1, CR2 and CD55 microdeletion/CHAPEL, FOXP3, PIK3CD, CD40L, ADA2). These 28 patients had 41 autoimmune diseases. Hematological AID was most common (50%)>GI (16%)>Endocrine (9%)>Skin (11%)>Rheumatological (7%)>Renal and neurological (1%). Hematological AID is most common manifestation in almost 75% of children with PIRD. Positive predictive value of abnormal immunological tests was 50% and sensitivity of 70%. JMF criteria had specificity of 100% in identifying PIRD but sensitivity was only 17%. Polyautoimmunity had a positive predictive value of 35% and sensitivity of only 40%. Avg age at initial presentation with autoimmunity in patients with underlying PIRD was 7.4 years vs 6.4 years in those without PIRD. 11/28 of these children were offered transplant out of whom 4 have successful transplants. 8/28 were started on sirolimus, 2/28 on abatacept, 3/28 on baracitinib, 2/29 on ruxolitinib after diagnosis that led to steroid withdrawal. 4 have died. Conclusion: 50% of children with AID have underlying PIRD. LRBA deficiency and STAT1 GOF were the most common PIRD. Age at presentation, number of autoimmunity, routine immunological tests and JMF criteria are not predictive of underlying PIRD. Early diagnosis with exome sequencing alters the prognosis and opens new therapeutic avenue.

Evaluating clinical factors for improved utilization of targeted gene panel testing for inborn errors of immunity in a U.S. tertiary care pediatric hospital

RationaleThere has been an increased use of targeted gene panels to evaluate inborn errors of immunity (IEI) due to increased availability and reduced costs. Refinements to clinical indications for targeted gene panels may improve yields for the test. MethodA retrospective chart review on 140 patients aged ≤18 years old with suspected IEI who had clinical targeted gene panel testing (Invitae®) for primary immune deficiency at a tertiary pediatric hospital in the U.S. Relevant clinical information and basic immunology labs, consisting of complete blood count, immunoglobulins, vaccine titers, immune competence, and other relevant lab tests, were evaluated. Additional patients with targeted gene panels sent over the course of 5 years are being reviewed to confirm these initial findings. ResultOf 140 patients (median age 3.9 years [IQR 1.6–9.5], 62% male, 85% Caucasian suspected of IEI and had the targeted gene panel sent, 9% had positive findings that led to a change in diagnosis and/or treatment plan. The most common indications for IEI workups in our cohort were infections (37%), organ-specific inflammation (30%), and periodic fevers (17%), Table 1. Of 52 patients with infections, 3 had pathogenic, or likely pathogenic variants in TNFRSF13B, CD40LG, and XLA genes. All patients with infections and normal clinical-based immunology testing had negative gene panels. Only one patient with organ-specific inflammation had a variant in STAT3 explaining her clinical features. Of 10 patients presenting with systemic autoimmune disease or polyautoimmunity, 5 had positive findings (STAT5B, TNFAIP3, NLRP12, COPA, and NLRC4 genes). Two of 24 patients with periodic fevers had variants in TNFAIP3 and MEFV, one had elevated inflammatory markers and one had positive family history. Of 9 patients who had WES after negative genetic panel, one patient had positive finding that explains his syndromic manifestations (PTEN).Table 1Primary Indication of sending targeted IEI panel and resultsPrimary Indications of sending targeted IEI gene panel N = 140)Number of patients with positive genetic testing that led to changes in diagnosis and/or treatment plans (n(%))Affected genes (each with n = 1)Infections (n = 52, 37%)3(6%)TNFRSF13B CD40LG XLAOrgan-specific inflammation (n = 42, 30%)1(2%)STAT3 LOF• Skin lesion (14)• Inflammatory bowel disease (9)• Cytopenias including ITP, Evan'ssyndrome and HLH (7)• Lymphadenopathy (3)• Others: enteropathy (3), pericarditis(2), arthritis (1), autoimmune hepatitis(1), endocrinologic disease (1), SNHL(1)Periodic fevers (n = 24,17%)2(8%)TNFAIP3 MEFVAbnormal newborn screening or1(9%)ATMabnormal immunology labs (n = 11, 8%)• Abnormal SCID screen (4)• Abnormal immunology labs (7)Systemic autoimmune disease or5 (50%)STAT5Bpolyautoimmunity (n = 10, 7%)TNFAIP3• Systemic autoimmune disease (4)NLRP12• Polyautoimmunity (6)COPANLRC4Family history (n = 1,1%)1 (100%)ATM• Pathogenic variant in ATMgene in identical twinIEI, inborn error of immunity; ITP, immune thrombocytopenia; HLH, hemophagocytic lymphohistiocytosis; SNHL, sensorineural hearing loss; SCID, severe combined immunodeficiency. ConclusionTargeted gene panel testing has the highest yield in patients with polyautoimmunity. Low yields of targeted gene panel were found in organ-specific inflammation, infections with normal clinical testing, and periodic fevers with normal inflammatory markers and a negative family history of IEI. Limitations included potentially missed cases from chart review.

Patterns of Interstitial Lung Disease in Egyptian Patients with Systemic Sclerosis: Relation to Disease Parameters.

Pulmonary involvement is the most common leading cause of morbidity and mortality associated with systemic sclerosis. Therefore, identifying the various patterns of pulmonary affection is crucial in the clinical management of these patients. In the current study, we aim to investigate the patterns of interstitial lung disease (ILD) associated with SSc patients (SSc- ILD) and their relation to serologic markers and clinical parameters. A cross-sectional study was undertaken on thirty-four adult SSc patients who met the 2013 ACR/EULAR criteria for SSc and Forty healthy controls of matched age and sex. The patients were subjected to history taking, clinical examination, skin assessment using the modified Rodnan Skin Score (mRSS), chest x-ray (CXR), pulmonary function test (PFTs), and high resolution computed tomography of the chest (HRCT). Routine laboratory tests were conducted in addition to immunologic tests and an enzyme-linked immunosorbent assay (ELISA) to determine the IL-33 level. ILD was found in 23 SSc patients (67.6%); 20 patients had diffuse type while 3 patients had limited type. Non-specific interstitial pneumonia (NSIP) was found in 56.5%, usual interstitial pneumonia (UIP) was found in 21.7%, pleuroparenchymal fibroelastosis (PPFE) was found in 8.7%, and organizing pneumonia (OP) with the mixed pattern was found in 13% of SSc patients. Additionally, the mean IL-33 level in SSc patients was 98±12.7 compared to 66.2±10.6 in the control group (p < 0.001), with ILD patients having a significantly higher level (101.7±13.4) than those without (90.4±6.2), and a strong positive correlation with mRSS. Even in asymptomatic patients with SSc, ILD is prevalent, with NSIP being the most common pattern. IL-33 could be considered a potential biomarker for predicting the presence of ILD in SSc patients.

Case Report: Suspected Hyperacute Rejection During Living Kidney Transplantation

We report a case of suspected hyperacute rejection during living kidney transplantation. A 61-year-old man underwent kidney transplantation in November 2019. Before the transplantation, immunologic tests revealed the presence of anti-HLA antibodies but not donor-specific HLA antibodies. The patient was intravenously administered 500 mg of methylprednisolone (MP) and basiliximab before perioperative blood flow reperfusion. After blood flow restoration, the transplanted kidney turned bright red and then blue. Hyperacute rejection was suspected. After the intravenous administration of 500 mg of MP and 30 g of intravenous immunoglobulin, the transplanted kidney gradually changed from blue to bright red. The initial postoperative urine output was good. On the 22nd day after the renal transplantation, the patient was discharged with a serum creatinine level of 2.38 mg/dL, and the function of the transplanted kidney gradually improved. In this study, non-HLA antibodies may have been a cause of the hyperacute rejection, which was managed with additional perioperative therapies.

Atypical Presentations of Hypomorphic X-Linked SCID

RationaleIL2RG mutations are associated with X-linked Severe Combined Immunodeficiency (X SCID). There is increasing awareness of Hypomorphic SCID associated with IL2RG variants; we present 3 novel mutations of this gene with variable presentations. MethodsChart review was performed for patients with hypomorphic SCID due to pathogenic IL2RG variants. Plasmablast differentiation was performed from peripheral blood mononuclear cells using CD40L and IL-21 stimulation for 6 days followed by staining for plasmablast markers (CD19+/CD27+/CD38+) and surface immunoglobulins. ResultsPatient 1 is a 7-year-old Honduran boy with history of recurrent sinopulmonary infections including recent CMV pneumonitis, bronchiectasis, chronic lung disease, food allergies, unilateral retinal detachment, and hydrocephalus s/p VP shunt. Immunologic testing showed elevated lymphocyte numbers with decreased memory B cells, normal immunoglobulins, absent vaccine responses, and poor proliferation to mitogens. Whole genome testing showed two mosaic mutations in IL2RG: c. 568C>T (20%), c. 589T>C (87%). He is on prophylaxis with azithromycin and trimethoprim/sulfamethoxazole, immunoglobulin, and awaiting definitive treatment. Patient 2 is a 10-year-old with recurrent sinopulmonary disease with bronchiectasis. He had normal TRECs, normal lymphocyte numbers with normal mitogen proliferation to PHA, normal immunoglobulin levels, but absent vaccine responses, and abnormal plasmablast differentiation (0.12% CD27+/CD38+ at day 6 post in vitro activation) and profoundly decreased expression of surface IgG and IgA in vitro. Genetic testing showed a hemizygous IL2RG c.32T>C mutation, as well as CFTR mutations (c.1972dup and c.1977_1985del, in cis). He is maintained on immunoglobulin replacement. Patient 3 is a 40-year-old who had recurrent infections beginning in childhood, and extranodal B-cell lymphoma at age 26 years. He had pan-lymphopenia, and genetic testing showed IL2RG c.982C>T, p.R328X. He underwent successful bone marrow transplantation from a matched sibling at age 36. ConclusionsHypomorphic X-SCID due to novel or mosaic variants in IL2RG can present with variable symptoms including malignancy and variable lymphocyte phenotype including normal T, B, and NK cell counts, and should be considered in males with opportunistic or persistent infections. [Display omitted]

The estimation of the toxic effects of «Complex Plus» agrochemical and perspective use in agriculture

use of agrochemicals strengthen health and environmental issues. To insure the safe use of new preparations, acute and sub-acute studies must to be done. &#x0D; In this study, the estimation of the toxic effects of “Complex Plus” formulation synthesized on the basis of imidacloprid and proposed as growth stimulator, insecticide and microelements complex simultaneously has been achieved. &#x0D; Material and methods. The oral and dermal LD50 have been established, sensitivity by sex, skin-irritating and allergic effects, effect on the mucous membranes (rats, rabbits) were studied. The results were processed by the method of variation statistics; standard errors, etc. were calculated by the method of probabilistic analysis of Litchfield–Wilcoxon in the modification of Prozorovsky. The values difference was estimated by two-tailed Student’s test (t-test) with significance level at p&lt;0.05.&#x0D; Results. The acute intoxication was manifested in some disorders of the central nervous system. Oral LD50 was 805±27 mg/kg bodyweight (II Class, WHO; IV class GOST 32419); dermal LD50&gt;2000 mg/kg bodyweight (III class, WHO; IV class GOST 32419). Sex sensitivity and skin-irritating effects were not revealed. The formulation had a moderate irritant effect on the mucous membranes of eyes (rabbits) and no sensitizing effect. Immunological tests in vitro were negative. &#x0D; Limitation. Acute toxicity and sensitizing effect of formulation was studied.&#x0D; Conclusion. Strict complying with the established agrotechnical requirements, hygienic regulations when using the proposed agrochemical will undoubtedly reduce the adverse effects of this formulation on the population and the environment, and will also contribute to development of agriculture in Armenia in the cost-effective way.

Evaluation of Five Non-Culture-Based Methods for the Diagnosis of Meningeal Sporotrichosis

Sporotrichosis is the main subcutaneous mycosis worldwide. Several complications, including meningeal forms, can be observed in immunocompromised individuals. The sporotrichosis diagnosis is time-consuming due to the culture's limitations. The low fungal burden in cerebrospinal fluid (CSF) samples is another important drawback in the diagnosis of meningeal sporotrichosis. Molecular and immunological tests can improve the detection of Sporothrix spp. in clinical specimens. Therefore, the following five non-culture-based methods were evaluated for the detection of Sporothrix spp. in 30 CSF samples: (i) species-specific polymerase chain reaction (PCR); (ii) nested PCR; (iii) quantitative PCR; (iv) enzyme-linked immunosorbent assay (ELISA) for IgG detection; and (v) ELISA for IgM detection. The species-specific PCR was unsuccessful in the diagnosis of the meningeal sporotrichosis. The other four methods presented substantial levels of sensitivity (78.6% to 92.9%) and specificity (75% to 100%) for the indirect detection of Sporothrix spp. Both DNA-based methods presented similar accuracy (84.6%). Both ELISA methods were concomitantly positive only for patients with sporotrichosis and clinical signs of meningitis. We suggest that these methods should be implemented in clinical practice to detect Sporothrix spp. in CSF early, which may optimize treatment, augment the chances of a cure, and improve the prognosis of affected individuals.

Detection of Hepatitis B Virus Genome with Mutations Outside the Major Hydrophilic Region in the Surface Antigen Isolated from Patients with Coexisting HBsAg and Anti-HBs

Background: The leading cause of mutations in the hepatitis B virus (HBV) genome is the high rate of nucleotide misincorporation during reverse transcription. Most mutations were found within the “a” determinant of the S gene’s major hydrophilic region (MHR). They resulted in escape mutants due to amino acid changes in the MHR. However, mutations outside the MHR can also trigger escape mutants. Objectives: This study focused on further molecular studies on the MHR of genotype D of HBV DNA isolated from patients with chronic HBV infection, together with the coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibodies (anti-HBs) in their serum samples. Methods: In this study, serum samples from 83 patients with chronic HBV infection were analyzed by serological and immunological tests for the concurrence of HBsAg and anti-HBs. In addition, the mutation in the HBV DNA was assessed by nucleotide sequencing of S genes within, upstream, and downstream of the MHR. Results: Among 83 patients with chronic HBV infection, the coexistence of HBsAg and anti-HBs were detected in 11 (13.25%) individuals. Mutations in eight amino acids of seven samples analyzed for nucleotide sequencing were observed at 27 different sites in three locations, namely upstream, within, and downstream of the MHR. The mutations affected the structure of the epitope and the appearance of an escape mutant. Conclusions: The results indicated that mutations downstream and upstream of the MHR play a role in the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection.

Хвороба Крона в дітей раннього віку. Складний шлях до діагнозу

Inflammatory bowel diseases (IBD) is a group of chronic diseases characterized by destructive non-specific immune inflammation of the intestinal wall. The main forms include Crohn's disease and ulcerative colitis. Currently, Crohn's disease is one of the most urgent problems of children's gastroenterology, which is due to the annual increase in morbidity, "rejuvenation" of the pathological process, difficulties of diagnosis treatment, and high risk in developing of complications. IBDs with very early onset of manifestation have an atypical or erased clinical picture, which makes timely diagnosis in this age group of patients much more difficult. Purpose - to describe own clinical observation of a case of Crohn's disease with a very early onset. Clinical case. Was presented an observation of a patient of 2 years and 7 months old with Crohn’s disease the feature of which was a severe course with pronounced lesion of the gastrointestinal tract. The results of clinical data, laboratory, instrumental and histological methods of research, the complex stages of diagnosing of Crohn’s disease, as well as the issues of the patient’s treatment were discussed. The peculiarity of the described case was the early onset of the disease, continuously relapsing course, frequent acute respiratory diseases accompanied with diarrheal syndrome, absence of some specific complaints and changes in biochemical and immunological tests, corticosteroid dependence and severe extraintestinal manifestations of Crohn’s disease (anemia of a mixed nature). The diagnosis of Crohn’s disease was made at the age of 1year and 9 months (1 year and 4 months after the appearance of the first symptoms), which was confirmed a year later after a repeat examination. Late diagnosis was caused by the variety of clinical manifestations, absence of clear symptoms of the disease at the first stages of observation. The research was carried out in accordance with the principles of the Declaration of Helsinki, informed consent of the child's parents was obtained for the research. No conflict of interests was declared by the authors.

Teaching NeuroImages: Spinal intramedullary cysticercosis

A 10-year-old boy was admitted to the hospital with decreased muscle strength in lower limbs. Physical examination revealed isolated spastic crural paraparesis. MRI of the thoracic spine demonstrated a cystic intramedullary lesion (figure 1). The patient underwent complete microsurgical resection of the lesion. Anatomopathologic report (figure 2) confirmed cysticercosis. Intramedullary cysticercosis is a rare parasitic infection caused by Taenia solium (0.7%–5.8% of all patients with neurocysticercosis).1 This presentation is usually underdiagnosed because, in degeneration phases, it is difficult to visualize the parasite in the MRI, mainly the scolex, and immunologic tests are negative due to intraparenchymal location.2

Positron Emission-Computed Tomography, Cryobiopsy versus Bronchoalveolar Lavage and Computed Tomography Findings for Interstitial Lung Disease: A Long-Term Follow-Up.

Background and Objectives: Interstitial lung diseases have always been an issue for pulmonary and rheumatology physicians. Computed tomography scans with a high-resolution protocol and bronchoalveolar lavage have been used along with biochemical blood tests to reach a diagnosis. Materials and Methods: We included 80 patients in total. First, all patients had their diagnosis with computed tomography of the thorax, serological/ immunological blood tests and bronchoalveolar lavage. However; after 3 months, all were divided into 2 groups: those who had bronchoalveolar lavage again and those who had cryobiopsy instead of bronchoalveolar lavage (40/40). Positron emission-computed tomography was also performed upon the first and second diagnosis. The patients' follow-up was 4 years from diagnosis. Results: Patients suffered most from chronic obstructive pulmonary disease (56, 70%), while lung cancer was rarely encountered in the sample (7, 9.75%). Age distribution ranged between 53 and 68 years with a mean value of 60 years. The computed tomography findings revealed 25 patients with typical diagnosis (35.2%), 17 with interstitial pulmonary fibrosis (23.9%) and 11 with probable diagnosis (11%). The cryobiopsy technique led to a new diagnosis in 28 patients (35% of the total sample). Patients who had a new diagnosis with cryobiopsy had a mean survival time of 710 days (<1460). Positron emission-computed tomography SUV uptake was positively associated with the cryobiopsy technique/new disease diagnosis and improved all respiratory functions. Discussion: Positron emission-computed tomography is a tool that can be used along with respiratory functions for disease evaluation. Conclusions: Cryobiopsy is a safe tool for patients with interstitial lung disease and can assist in the diagnosis of interstitial lung diseases. The survival of patients was increased in the cryobiopsy group versus only bronchoalveolar lavage for disease diagnosis.