- Discriminant value of IEL counts and distribution pattern through the spectrum of gluten sensitivity: a simple diagnostic approach. [Journal Article]
- VAVirchows Arch 2018 Aug 09
- Intraepithelial lymphocytosis (IELosis) with or without villous abnormality is a characteristic feature of gluten sensitivity (GS) including celiac disease (CD) and non-celiac-GS, although various co...
Intraepithelial lymphocytosis (IELosis) with or without villous abnormality is a characteristic feature of gluten sensitivity (GS) including celiac disease (CD) and non-celiac-GS, although various conditions may also be associated with IELosis. In order to distinguish GS from the other causes of IELosis, a threshold for IEL counts is necessary. We aimed to determine a cut-off value for IELs and monitor its value in the spectrum of GS in a large cohort. For this purpose, the duodenal biopsies from four groups of individuals including Types 1 (n = 88) and 3 (n = 92) CD, non-CD IELosis (n = 112), and control (n = 82) cases, all strictly defined by their clinical, laboratory, and serologic features, were evaluated. The number of IELs/100 enterocytes and their distribution pattern on H&E- and CD3-immunostained sections were assessed for each group. Kruskal-Wallis test and ROC curve analysis for discriminant value were employed for statistics. The IEL counts showed an increasing trend through the spectrum of mucosal pathology including controls (12.06; 21.40), non-CD IELosis (28.62; 39.46), Type 1 CD (49.27; 60.15), and Type 3 CD (58.53; 71.74) both on H&E- and CD3-immunostained sections, respectively (p < 0.001). ROC analysis revealed 20.5 on H&E and 28.5 on CD3 as the IEL cut-off values with a sensitivity of 95.9 and 87.7% and a specificity of 98.8% and 93.9%, respectively, for controls. IELs showed a diffuse distribution pattern per biopsy piece and per villus (90.9%, 100%, respectively) in nearly all of Type 1 CD cases (p < 0.001). An IEL cut-off value of 20.5 on H&E together with a diffuse distribution pattern seem to be the most discriminant features for the diagnosis of CD, even for the milder forms of the disease.
- Cell mediated immune response in goats after experimental challenge with the virulent Brucella melitensis strain 16M and the reduced virulence strain Rev. 1. [Journal Article]
- VIVet Immunol Immunopathol 2018; 202:74-84
- Brucella melitensis is the etiologic agent of brucellosis in small ruminants and a common cause of disease in humans. While the protective immune response against this pathogen has been well studied ...
Brucella melitensis is the etiologic agent of brucellosis in small ruminants and a common cause of disease in humans. While the protective immune response against this pathogen has been well studied in the mouse model, little is known of the immune response triggered by B. melitensis infection in natural hosts. The objective of the present study was to evaluate the caprine immune response over the course of infection with virulent B. melitensis strain 16 M and reduced virulence vaccine strain Rev. 1. Pregnant goats were infected at 11-14 weeks of gestation with 8 × 106 or 8 × 107 CFU of B. melitensis. Changes in granulocyte, monocyte, and mononuclear cell numbers were monitored by flow cytometry. Proliferative and functional responses of CD4+ T cells and WC1+ γδ T cells were also studied. B. melitensis 16 M infection triggered a pro-inflammatory response characterized by increased numbers of granulocytes, monocytes, and lymphocytes. The relative lymphocytosis was comprised of increases in CD4+ but not WC1+ T cell types in most animals. Little proliferative response was observed in Rev. 1-infected goats. Analysis of lymphocyte function suggested a degree of potential CD4+ T cell anergy, with low levels of CD25 expression and unresponsiveness to mitogen stimulation noted post-infection. The components of the protective response elicited by the Rev. 1 vaccine strain remain undefined. The study suggests a potential WC1+ γδ T cell mediated response, with high percentages of γδ T cells found to produce IFN-γ at various time points over the course of Brucella infection.
- Sensory ganglionopathy associated with drug-induced hypersensitivity syndrome caused by mexiletine. [Journal Article]
- BCBMJ Case Rep 2018 Aug 04; 2018
- Although various causes are reported for sensory ganglionopathy, drug-induced hypersensitivity syndrome (DIHS) has not been considered a possibility. We describe a 70-year-old woman, previously admin...
Although various causes are reported for sensory ganglionopathy, drug-induced hypersensitivity syndrome (DIHS) has not been considered a possibility. We describe a 70-year-old woman, previously administered mexiletine hydrochloride for 4 weeks, who presented with systemic oedematous erythema and subacute progressive gait disturbance. Evaluation revealed lymphadenopathy with atypical lymphocytosis and eosinophilia, and human herpesvirus 6 (HHV-6) reactivation. Neurological examination indicated the almost complete loss of joint positional sense in her extremities; her tendon reflex was lost and there was marked pseudoathetosis and Romberg's sign. Skin biopsy revealed spongiosis with lymphocyte infiltration. Based on these findings, we diagnosed acute sensory ganglionopathy secondary to DIHS. Although her DIHS-induced symptoms subsided after methylprednisolone treatment, partial remission of sensory ganglionopathy occurred, even after subsequent intravenous immunoglobulin therapy. This case suggests the possibility that reactivation of HHV-6 may be involved in the pathomechanism of sensory ganglionopathy.
- Immunophenotypic Profile and Clinical Outcome of Monoclonal B-cell Lymphocytosis in Kidney Transplantation. [Journal Article]
- CTClin Transplant 2018 Aug 03; :e13338
- Monoclonal B-cell lymphocytosis (MBL) is a lymphoproliferative disorder characterized by clonal expansion of a B-cell population in peripheral blood of otherwise healthy subjects. MBL is divided into...
Monoclonal B-cell lymphocytosis (MBL) is a lymphoproliferative disorder characterized by clonal expansion of a B-cell population in peripheral blood of otherwise healthy subjects. MBL is divided into CLL (chronic lymphocytic leukemia)-like, atypical CLL-like and non-CLL MBL. The aim of this study was to evaluate immunophenotypic characteristics and clinical outcomes of MBL in kidney transplant (KT) recipients. We retrospectively evaluated 593 kidney transplant (KT) recipients in follow-up at our center. Among them, 157 patients underwent peripheral blood flow-cytometry for different clinical indications. A 6-color panel flow-cytometry was used to diagnose MBL. MBL was detected in 5 of 157 KT recipients. Immunophenotypic characterization of MBL showed four cases of non-CLL MBL and one case of CLL-like MBL. At presentation, median age was 65 years (range 61-73). After a median follow-up of 3.1 years (95%CI; 1.1-5) from diagnosis, patients did not progress either to CLL or lymphoma. The disorder did not increase the risk of malignancy, severe infections, graft loss and mortality among our KT recipients. Surprisingly, all cases were also affected by concomitant monoclonal gammopathy of undetermined significance, which did not progress to multiple myeloma during follow-up. In conclusion, our data suggest that MBL is an age-related disorder, with non-CLL MBL being the most common subtype among KT recipients. This article is protected by copyright. All rights reserved.
- The Frequency and Prognostic Value of Neutrophilia in Chronic Lymphocytic Leukemia. [Journal Article]
- ARAnticancer Res 2018; 38(8):4731-4734
- CONCLUSIONS: The presence of neutrophilia without monocytosis before treatment appears to be associated with a more favorable prognosis in CLL. These observations still need to be confirmed and validated in a larger cohort of patients.
- Progressive peripheral CD8+ T lymphocytosis complicated by pure red cell aplasia following immunosuppressive therapy for thymoma-associated myasthenia gravis. [Journal Article]
- IIInt Immunopharmacol 2018 Jul 26; 63:14-18
- We herein report a unique case of type B2 thymoma-associated myasthenia gravis which was ameliorated by immunosuppressive therapy in combination with chemotherapy. However, the patient subsequently d...
We herein report a unique case of type B2 thymoma-associated myasthenia gravis which was ameliorated by immunosuppressive therapy in combination with chemotherapy. However, the patient subsequently developed pure red cell aplasia and marked lymphocytosis after additional chemotherapy aimed at improvement of thymoma. While a separate immunosuppressive regimen was effective for anemia, lymphocytosis was exacerbated. The biopsied thymoma specimen contained CD4+, CD8+, and CD4+/CD8+ T cells, some of which were CD3-, suggesting immature thymocytes. In contrast, majority of the peripheral lymphocytes were polyclonal CD3+/CD8+/T cell receptor (TCR)αβ+ T cells. The CD4/CD8 ratio in the present patient might be affected by immunosuppressive agents, resulting in CD8+ T cell expansion associated with pure red cell aplasia. Although several cases of thymoma accompanied by peripheral T cell lymphocytosis were reported, marked CD8+ T cell proliferation is extremely rare.
- A significant proportion of patients with primary central nervous system lymphoma harbor clonal bone marrow B-cells. [Journal Article]
- LLLeuk Lymphoma 2018 Jul 22; :1-7
- Clonal bone marrow (BM) B-cell populations are a common finding in patients with suspected primary central nervous system lymphoma (PCNSL). To assess their clinical significance, benign monoclonal B-...
Clonal bone marrow (BM) B-cell populations are a common finding in patients with suspected primary central nervous system lymphoma (PCNSL). To assess their clinical significance, benign monoclonal B-cell lymphocytosis (MBL) needs to be differentiated from concomitant BM involvement, since patients with secondary central nervous system lymphoma (SCNSL) generally require more intensive treatment directed also at the component outside the central nervous system (CNS). Here, we retrospectively analyzed BM samplings in 51 patients with suspected PCNSL. We found clonal B cell populations in 8 of 51 cases (16%) by flow cytometry. None of these eight cases had BM involvement by high-grade lymphoma. No lymphoma relapses outside the CNS were recorded. Together, our data points at a significant percentage of patients with suspected PCNSL harboring clonal BM B-cells, which in this patient group always represented benign MBL. Failure to differentiate these populations from systemic lymphoma involvement may result in overtreatment of patients.
- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Lymphadenopathy is a common abnormal finding during the course of the physical exam in general medical practice. Patients and physicians have varying degrees of associated anxiety with the finding of...
Lymphadenopathy is a common abnormal finding during the course of the physical exam in general medical practice. Patients and physicians have varying degrees of associated anxiety with the finding of lymphadenopathy as a small number of cases can be caused by neoplasm or infections of consequence, for example, HIV or tuberculosis (TB). However, it is generally recognized that the majority of lymphadenopathy, both localized and generalized, is of benign, self-limited, etiology. A clear understanding of lymph node function, location, description, and the etiologies of their enlargement is important in the clinical decisions of which cases need rapid and aggressive workup, and which need only be observed. The lymph node functions as an antigen filter for the reticuloendothelial (RE) system of the body. It consists of a multi-layered sinus that sequentially exposes B-cell lymphocytes, T-cell lymphocytes, and macrophages to an afferent extracellular fluid. In this way, the immune system can recognize and react to foreign proteins and mount an immune response or sequester these proteins as appropriate. In the course of this reaction, there is some multiplication of the responding immune cell line, and thus, the node itself increases in size. It is generally held that a node size is considered enlarged when it is larger than 1 cm. However, the reality is that "normal" and "enlarged" criteria vary depending on the location of the node and the age of the patient. For example, children younger than 10 years of age have more hypertrophic immune systems and nodes up to 2 cm can be considered normal in some clinical situations yet, an epitrochlear node of above 0.5 cm is considered pathological in an adult. The pattern, distribution, and quality of the lymphadenopathy can provide much clinical information in the diagnostic process. Lymphadenopathy occurs in 2 patterns: generalized and localized. Generalized lymphadenopathy entails lymphadenopathy in 2 or more non-contiguous locations. Localized adenopathy occurs in contiguous groupings of lymph nodes. Lymph nodes are distributed in discrete anatomical areas, and their enlargement reflects the lymphatic drainage of their location. The nodes themselves may be tender or non-tender, fixed or mobile, and discreet or "matted" together. Concomitant symptomatology and the epidemiology of the patient and the illness provide further diagnostic cues. A thorough history of any prodromal illness, fever, chills, night sweats, weight loss, and localizing symptoms can be very revealing. Additionally, the demographic particulars of the patient, including age, gender, exposure to infectious disease, toxins, medications, and their habits may provide further cues. As evidenced above, the critical step in evaluation for adenopathy is a careful history and focused physical exam. The extent of the history and physical is determined by the clinical presentation of the patient. For example, a patient with posterior cervical adenopathy sore throat and tremendous fatigue needs only a careful history, cursory examination and a mono test, while a person with generalized lymphadenopathy and fatigue would require a much more extensive investigation. Generally, the majority of the lymphadenopathy is localized (some site a 3:1 ratio), with the majority of that being represented in the head and neck region (again some site a 3:1 ratio). It also is accepted, that all generalized lymphadenopathy merits clinical evaluation and the presence of "matted lymphadenopathy" is strongly indicative of significant pathology.Examination of the patient's history, physical examination, and the demographic in which they fall can allow the patient to be placed into 1 of several different accepted algorithms for workup of lymphadenopathy. The use of these cues and selection of the correct arm of the algorithm allows for fairly rapid and cost-effective diagnosis of lymphadenopathy including determination when it is safe to observe. Algorithmic Analysis of Lymphadenopathy After a history and physical examination are completed, lymphadenopathy is placed into 3 categories: 1. "Diagnostic" such as strep pharyngitis or upper respiratory tract disease in which case the course of action is to treat the condition. 2. "Suggestive" such as mononucleosis lymphoma or HIV wherein the history and physical strongly suggestive diagnosis specific testing is performed and if positive the action is to treat the condition. 3. "Unexplained" where the lymphadenopathy is divided into generalized lymphadenopathy and localized lymphadenopathy. For unexplained localized lymphadenopathy, a review of history, a regional exam and the epidemiological clues are used to separate patients into lower (no risk of malignancy or serious disease) versus higher risk for serious disease or malignancy categories. If the patient is at no risk for malignancy or serious illness, the reasonable course of action is to observe the patient for 3 to 4 weeks to see if the lymphadenopathy resolves or improves. In which case, the clinician is safely cleared to follow the patient. If the lymphadenopathy does not resolve or improve, the next step is to obtain a biopsy. If the patient is judged to have a risk for malignancy or serious illness the procedure is to proceed immediately to biopsy. For unexplained generalized lymphadenopathy, the key to diagnosis is a history to evaluate for suspected causes. Initial search would be questioning for a mononucleosis-type syndrome such as evidenced by fever atypical lymphocytosis and malaise included in these differentials would be Epstein-Barr virus, cytomegalovirus, toxoplasmosis, and (especially in the case of a flu-like illness and her rash) the initial stages of an HIV infection. The second step in the evaluation of unexplained generalized lymphadenopathy involves a careful review of epidemiological cues. Included in the epidemiological cues would be: 1. Infectious disease exposure. 2. Animal exposure. 3. Insect bites. 4. Recent travel. 5. Complete medication history. 6. Personal habits-smoking, consumption of alcohol, consumption of drugs-special attention to a history of IVTA, high-risk sexual behavior. 7. Consumption of undercooked food/untreated water. Although there is no "cookbook" for the laboratory evaluation of generalized unexplained lymphadenopathy, initial steps are to obtain a complete blood count (CBC) with a manual differential and EBV serology. If non-diagnostic, the next steps would be PPD placement, RPR, chest x-ray, ANA, hepatitis B surface antigen, and HIV test. Again if any of the above are positive, appropriate treatment can be initiated. In the presence of negative serological examinations and radiological examinations and or significant symptomology, a biopsy of the abnormal node is the gold standard for diagnosis.Statistics concerning lymphadenopathy are not accurate as the great majority of lymphadenopathy is caused by a non-reportable illness and thus not reported or taken into account. This results in a statistical bias, or skew, toward the reportable causes of lymphadenopathy: malignancies, HIV, tuberculosis, and sexually transmitted diseases (STDs). Citations in the recent literature for general medical practice indicate that less than 1% of people with lymphadenopathy have malignant disease most often due to leukemia and younger children Hodgkin disease in adolescence non-Hodgkin disease and chronic lymphocytic leukemia (CLL) in adults. It has been reported the general prevalence of malignancy is 0.4% in patients under 40 years and around 4% in those older than 40 years of age seen in a primary care setting. It is reported that the prevalence rate of neoplastic disease rises to near 20% in referral centers and rises to 50% or more in patients with initial risk factors.
- Clonal T-cell Large Granular Lymphocytic Disorders Manifesting in Patients with HIV-1 Infection: Case Series and Review of the Literature. [Journal Article]
- MJMediterr J Hematol Infect Dis 2018; 10(1):e2018036
- We report five patients with human immunodeficiency virus-1/acquired immunodeficiency syndrome (HIV-1/AIDS) who developed T-cell large granular lymphocytic proliferation (T-LGLP) or leukemia (T-LGLL)...
We report five patients with human immunodeficiency virus-1/acquired immunodeficiency syndrome (HIV-1/AIDS) who developed T-cell large granular lymphocytic proliferation (T-LGLP) or leukemia (T-LGLL). None of the patients fulfilled criteria for diagnosis of diffuse infiltrative lymphocyte syndrome (DILS) or HIV-associated CD8+ lymphocytosis syndrome at the time of diagnosis of LGL. The immunophenotype of malignant T-cells was identical in three patients with co-expression of CD3, CD8, CD57, and T-cell receptor (TCR) alpha/beta. Three out of five patients were also diagnosed with clonal disorders of B-cell origin including diffuse large B-cell lymphoma, Burkitt's lymphoma, and monoclonal gammopathy of undetermined significance (MGUS). Two patients developed cytopenias due to T-LGLL prompting initiation of therapy. Our study suggests that chronic viral infection with HIV can contribute to the evolution of T-LGLP. Clinical and laboratory characteristics of T-LGLP associated with HIV-1/AIDS resemble those of immunocompetent patients.
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- Risk of Diffuse Infiltrative Lymphocytosis Syndrome in HIV-Infected Patients: A Nationwide Population-Based Cohort Study. [Journal Article]
- JAJ Acquir Immune Defic Syndr 2018 Jul 09
- CONCLUSIONS: DILS is a rare disease found in PLWHA. Hypertension is a risk factor for incident DILS, and HAART could affect the pathogenesis of DILS. Zalcitabine was the only antiretroviral agent found to increase the risk of DILS.