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PubMed2025

Clinical and laboratory profiles of Oropouche virus disease from the 2024 outbreak in Manaus, Brazilian Amazon.

BACKGROUND: The 2024 Oropouche virus (OROV) outbreak in Brazil raised public health concerns due to its unprecedented rapid spread, high incidence, and potential neurological complications. OROV symptoms overlap with locally endemic arbovirus diseases, like dengue virus (DENV), complicating diagnosis. The study aimed to compare clinical, laboratory, and immunological profiles in OROV and DENV cases, crucial for improving diagnosis and management. METHODS: This study analyzed 51 OROV and 78 of DENV cases consecutively enrolled in Manaus, Amazonas, Brazil, and monitored for 28 days. OROV diagnosis was performed by real-time PCR (RT-PCR) using serum and urine samples. OROV RT-PCR positive samples were genotyped. A paired Plaque Reduction Neutralization Test (PRNT) was conducted on samples collected at D1 and D28. Patients with a&#x2009;&#x2265;&#x2009;4-fold increase in neutralizing antibody titer between D1 and D28 were considered OROV-positive. Clinical manifestations, hematology, biochemistry, and cytokine profiles were analyzed. Statistical analysis included comparison between OROV and DENV patients. RESULTS: Genome sequencing of OROV isolates confirmed presence of a previously reported novel reassortment event, consistent with ongoing localized transmission. Urine RT-PCR demonstrated low positivity compared to serum samples. The paired PRNT increased sensitivity in 45%. Clinically, OROV infection was associated with significantly higher frequencies of severe headache, myalgia, arthralgia, and rash compared to DENV infection (p&#x2009;<&#x2009;0.001). Elevated alanine aminotransferase (ALT) levels were also observed in OROV patients (p&#x2009;<&#x2009;0.001). Immunologically, OROV infection induced significantly increased levels of acute-phase CCL11 (eotaxin), CXCL10, IFN-&#x3b3;, IL-1RA, and IL-10, which declined by day 28, while IL-5 increased during recovery. In contrast, DENV patients exhibited elevated levels of CCL2, G-CSF, and CCL3 in recovery phase. CONCLUSION: OROV symptoms overlap with DENV underscores the need for syndromic diagnostic approach in endemic regions. Continued genomic surveillance and expanded clinical studies are vital to assess long-term consequences. Given OROV's expanding geographic range, targeted public health measures are essential to mitigate future outbreaks and better understand its pathophysiology.

Humans↗
PubMed2005

Cytokine profile of iron-laden macrophages: implications for cellular magnetic resonance imaging.

Superparamagnetic iron oxide (SPIO/USPIO) particles are a promising new tool to label cells for in vivo monitoring of their migration into the nervous system by magnetic resonance imaging (MRI). Upon systemic application, SPIO/USPIO particles are preferentially internalized by macrophages. It is unclear whether this affects their immunological profile. We tested the cytokine production of rat and mouse macrophages in vitro and found that internalization of SPIO/USPIO shifted macrophages towards an anti-inflammatory, less responsive phenotype by enhancing interleukin (IL)-10 and inhibiting tumor necrosis factor (TNF)-alpha production. During macrophage interaction with T-cells IL-12p40 secretion was inhibited. Based on our in vitro findings, potential immunomodulatory effects of SPIO/USPIO particles in vivo warrant further investigation.

Animals↗
PubMed2002

Autotransplantation for treatment of severe splenic lesions.

The aim of the study was to evaluate clinical and laboratory variables in patients undergoing spleen autotransplantation. We studied 29 patients with severe trauma of the spleen and its pedicle. Of these, 20 underwent autotransplantation (group I) and 9 underwent total splenectomy without preservation of splenic tissue (group II). Twenty-two additional subjects with an intact spleen were used as controls (group III). Immediate and late postoperative complications were investigated. Laboratory counts were performed during the late postoperative period (red blood cells, hemoglobin, white blood cells, platelets, and Howell-Jolly bodies). To investigate the immunological profiles of patients we performed B- and T-lymphocyte counts and determined IgA, IgG, and IgM levels. All patients underwent splenic scintigraphy with technetium 99m sulfur colloid. Groups I and III did not present abnormal blood bodies, and their hematological and immunological patterns were normal. Group II showed increased numbers of Howell-Jolly bodies and low IgM levels. Splenic scintigraphy indicated the viability and filtering function of the splenic remnant in group I. Autotransplantation is a good option to maintain splenic function when total splenectomy is necessary.

Journal Article↗
PubMed2002

Immunophenotypic profile of tumor infiltrating lymphocytes in medullary carcinoma of the breast.

Medullary carcinoma (MC) of the breast is considered to carry a more favorable prognosis than other subtypes of infiltrating ductal carcinoma. This is a biological paradox because its clinical behavior contrasts with its anaplastic morphology. MC is characterized by a dense lymphocytic infiltrate. In this study, we determined the immunological profile of tumor infiltrating lymphocytes (TILs) in MC by CD20 (L26), CD8, and CD45RO (UCHL 1) immunostaining on paraffin-embedded sections. We examined 14 cases of typical MC (TMC), 15 cases of atypical MC (AMC) classified according to Ridolfi criteria (1977) and 19 cases of poorly differentiated infiltrating ductal carcinoma (PDC-NOS). TILs were quantified separately into cells infiltrating tumor nests (intraepithelial) and cells infiltrating tumor stroma (stromal). The number of CD8 positive and CD20 positive cells infiltrating tumor nests and tumor stroma were significantly increased in TMC and AMC as opposed to the PDC-NOS group. There was a loss in the number of CD45RO positive cells, both intraepithelial and stromal, in TMC and AMC as opposed to the PDC-NOS group. We conclude that MC tumor lymphocytic infiltrate demonstrates a mixed-T cytotoxic (CD8+) and B cell (CD20+)-immunophenotypic profile. This might in part explain the improved clinical outcome of the disease.

Antigens, CD20↗
PubMed1981

Kidney transplantation by use of splenectomy and transfusions, cadaver haplotype matching, suppressor cell assays, and T-cell monitoring.

We attempted to modulate several determinants of the host immunologic profile to improve kidney transplant survival: (1) genotype matching of the cadaver donor with the recipient, (2) assessment in recipients of living related donors (LRD) for predisposition to generate suppressor cells in mixed lymphocyte culture (MLC), (3) pretransplant splenectomy and transfusions, and (4) posttransplant immunologic monitoring. Between January, 1979, and July, 1980, 48 primary renal transplants were performed and followed up between 6 and 24 months. Pretransplant splenectomy was performed, and transfusions were administered in 38 of 48 and 48 of 48 patients, respectively. Donors and recipients of 10 of 11 cadaveric transplants were genotyped and selected for one HLA haplotype identity. All 10 proved to also be one DR antigen matches. There were no cadaveric kidney losses, but one surgical antibody to T cell subtest were used to modulate rejection therapy. The LRD group (n = 37) included 13 HLA-identical, seven haploidentical low MLC reactors, and 17 haploidentical high MLC reactors. Three deaths occurred (diabetes and myocardial infarction, stroke, and pancreatitis). A three-component coculture assay was used in the LRD group before transplantation to determine the capacity to generate specific and nonspecific MLC suppressor cells. Suppressor cells were seen in 17 patients given standard immunosuppression postoperatively without rejection episodes. However, in 20 patients incapable of generating suppressor cells, seven biopsy-proved rejection episodes occurred. There were no kidney losses, with 44 of 48 surviving recipients demonstrating normal renal function.

Adolescent↗
PubMed1984

Differential effects of the mottled yellow and pseudoagouti phenotypes on immunocompetence in Avy/a mice.

Whereas genetic factors are known to influence both susceptibility to carcinogens and the capacity to respond to specific antigenic stimuli, little is known regarding the influence of phenotype per se. With this in mind, we utilized (YS x VY)F1 hybrid mice consisting of genetically identical (Avy/a) but phenotypically distinct (mottled yellow and pseudoagouti) mice as well as congeneic (a/a) black mice to evaluate immunocompetence as a function of genotype and phenotype. Mottled yellow Avy/a mice, which are fat and have increased susceptibility to neoplasia, presented an immunologic profile characterized by decreased antibody response to the T-cell-dependent immunogen tetanus toxoid, enhanced antibody response to the T-cell-independent immunogen type III pneumococcal polysaccharide, decreased (unadjusted) rates of carbon clearance, and increased levels of serum IgA. In contrast, pseudoagouti Avy/a mice were immunologically comparable to black a/a mice. The data demonstrate that differences in phenotypic expression between genetically identical mice may significantly alter immune function.

Alleles↗
PubMed1989

Study of lymphocyte populations and natural killer activity in severe aplastic anaemia.

Thirty-one patients (pts) with aplastic anaemia (AA) were studied whose probable etiology were: idiopathic (16 pts), nocturnal aroxysmal haemoglobinuria (NPH) (2 pts), benzene (4 pts), agrotoxics (5 pts), pharmaceutical drugs (2 pts) and insecticides (2 pts). A decrease in total lymphocyte counts was seen in 10 pts belonging mainly to the NPH and pharmaceutical drug groups, whereas, in the benzene group the opposite was found. B cell levels were low in 9 out of 20 pts. T cell levels varied, the majority of patients had normal levels, 13 presented low levels and 4 had increased numbers. CD4 levels were low in 14 pts and T cell numbers were compensated in some by an increase in CD8 cells. Our results show that there is a great heterogeneity among the patients and there might be differences in the immunological profile of aplastic anaemia depending on the causative agent of the disease.

Adult↗
PubMed2003

HPV subtypes and immunological parameters of cervical cancer in Iceland during two time periods, 1958-1960 and 1995-1996.

OBJECTIVE: Cervical cancer is a disease caused in part by an infection with an oncogenic subtype of human papillomavirus (HPV). In this study we analysed all cervical cancer samples diagnosed in Iceland during two periods, 1958-1960 and 1995-1996, and asked whether significant changes in viral or immunological parameters had occurred over a period that spanned both significant changes in sexual attitude and the implementation of organized screening for cervical cancer. METHODS: Samples from 47 patients (46 squamous cell carcinomas (SCC) and 1 adenosquamous carcinoma (ASC)) in the first period and 30 patients (20 SCC, 4 ASC, and 6 adenocarcinomas (AC)) in the later period were analysed for viral subtype and expression of Fas, FasL, MHC class I, p53 and apoptosis. RESULTS: AC and ASC are proportionately much more common today than 40 years ago (30% vs 2%). The distribution of HPV in cervical cancer is similar in both periods, with HPV16 found in 75% and HPV18 in 13% of cases. Other HPV types found were 31,33,45, and 59. No significant differences were found in the immunological profiles of tumors from the two periods except that a higher fraction of SCC in the later period stained positive for FasL. When SCC are compared with AC/ASC, the latter have less expression of MHC class I, less expression of Fas, and stronger FasL expression. CONCLUSIONS: AC/ASC tumors show some immunological features that suggest that they are more resistant to immune attack than SCC.

Adenocarcinoma↗
PubMed1992

Potential role of immunomodulators for treatment of phlebovirus infections of animals.

Rift Valley fever (RVFV) is a major phlebovirus-induced epizootic disease of domestic animals (primarily cattle and sheep) in Africa. No therapies for the disease are known. A related phlebovirus, Punta Toro virus (PTV), has been adapted to induce an RVFV-like disease in C57BL/6 mice. This PTV infection has been used as a model for RVFV because it is reasonably safe and does not require high-level biologic containment. The infection model has been used to study the potential role of immunomodulating substances as therapies. A spectrum of immunomodulators has been studied; those immunomodulators most capable of preventing death and other disease manifestations are ampligen, bropirimine, poly (ICLC), AM-3, P-136, and 7-thia-8-oxoguanosine. An immunologic parameter common to all these substances has been their ability to induce interferon. Timing studies have indicated that these active substances may be administered therapeutically as well as prophylactically to inhibit markedly the progress of the disease. Further work is needed in the development of these materials for use in treating viral infections in domestic animals. As a next step, studies need to be run to compare the immunologic profiles induced by each substance in domestic animals and in mice.

Adjuvants, Immunologic↗
PubMed1992

Comparative immunoreactive profiles of Japanese and American patients with primary biliary cirrhosis against mitochondrial autoantigens.

Primary biliary cirrhosis (PBC) has been described among various ethnic and racial populations in all parts of the world. However, the incidence and prevalence of PBC varies considerably in different geographic areas. It has the highest frequency in Northern Europe, is considerably lower in Japan and still lower in other parts of Asia. There has not hitherto been a detailed immunological profile of antimitochondrial antibodies according to geographic region. We have used recombinant or purified preparations from the 2-oxo-acid dehydrogenase enzyme complexes, the major mitochondrial autoantigens in PBC (PDC-E2, BCOADC-E2, OGDC, protein X and PDC-E1 alpha) to compare the reactivity of sera from either similarly staged sera from Japanese (n = 23) or American-Caucasian patients (n = 39) with PBC. In all cases, the first available sera following diagnosis was selected. Interestingly, only 65% of Japanese patients reacted by ELISA with PDC-E2 compared with more than 95% of the North American group. Moreover, the level of enzyme-inhibitory antibodies to PDC was lower in the Japanese. Our findings prompt the need for characterization of specific susceptibility genes and environmental factors in various parts of the world to clarify the etiology of PBC.

Antigen-Antibody Reactions↗
PubMed2000

Single lesion paucibacillary leprosy: baseline profile of the Brazilian Multicenter Cohort Study.

In Brazil, there is little information about the clinical and epidemiological characteristics of paucibacillary, single skin lesion leprosy patients (SSL-PB). Only recently has the official notification system distinguished leprosy patients with a single lesion as a clinical entity, for whom the single-dose ROM (rifampin, ofloxacin and minocycline) regimen has been recommended. In this paper, we describe the baseline clinical features and the immunological background of a multicenter cohort of SSL-PB leprosy cases enrolled between December 1997-1998. Patients were recruited at health centers located in the following regions: Southeast = Rio de Janeiro; North = Amazon and Rondônia states and Center-West = Goiás state. Eligible cases were newly detected, untreated single-lesion leprosy patients without thickened nerve involvement, and were assessed by clinical, bacilloscopic and histopathological exams. The Mitsuda skin test and anti-PGL-I serology (ELISA) were also performed. Of the 299 SSL-PB leprosy patients, 259 (86.6%) fulfilled the criteria for single-dose ROM intervention. Our results showed that patients recruited from different sites had similar features, considering the clinical and immunological profiles. There was a predominance of adults (mean age 32.4; S.D. = 16.0), and a BCG scar was detected in 76.7% of the children (< or = 15 years old). Only 7 cases were diagnosed as the multibacillary type, representing less than 3% of the patients being misclassified. Our data indicate that in Brazil SSL-PB case ascertainment based on clinical and bacilloscopic criteria can be accurately defined under a routine control program; 75.0% of SSL-PB cases were Mitsuda positive (> or = 5 mm) and seropositivity for anti-PGL-I was detected in 17.3% of the patients. These data are compatible with effective cell-mediated immunity and low bacillary load, suggesting favorable clinical outcomes for most SSL-PB participants of this cohort.

Adolescent↗
PubMed1984

Critical analysis of T cell subset and function evaluation in patients with persistent generalized lymphadenopathy in groups at risk for AIDS.

In order to determine whether there exists a distinct immunological profile that discriminates between healthy homosexual men and those expressing persistent generalized hyperplastic lympadenopathy GHL and which of the observed abnormalities in GHL would be most indicative of patients who would eventually develop AIDS, we evaluated T lymphocyte subset and in vitro proliferative responses. The respective profiles of 44 symptom free homosexual men (HC), 42 patients with GHL and 30 cases of AIDS were compared to that of blood bank volunteers (BBV) and to each other, using stepwise discrimination analysis. HC, GHL and AIDS patients demonstrated upon their first investigation varying degrees of the same type of abnormal immunological characteristics. The percentage of OKT4+ cells was the most discriminant variable between BBV and HC, GHL or AIDS. GHL was distinguished from HC primarily by a higher percentage of OKT8+ cells and from AIDS by higher T lymphocyte counts, while the OKT4+ cell count discriminated between AIDS and HC. However, none of these major discriminant variables could classify correctly more than 71% within the HC and the two patient groups. Thus, there exists a continuity between GHL and AIDS in the range of observed immunological abnormalities without clearcut boundaries. This, together with the existence of abnormal background values in HC will not permit a single investigation of T lymphocyte immune parameters to provide substantial diagnostic and prognostic evidence.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Th1/Th2 cytokine imbalance in patients with Sjögren syndrome secondary to hepatitis C virus infection.

OBJECTIVE: To investigate if the serum immunologic profile, as delineated by serum circulating levels of Th1/Th2 cytokines and autoantibodies, is different in patients with Sjögren syndrome (SS) with and without hepatitis C virus (HCV) infection. METHODS: This study included 20 patients with HCV-related SS and 47 consecutive patients with primary SS. All fulfilled 4 or more of the modified 1996 European criteria for SS. Serum levels of interleukin (IL)-2 (pg/mL), srIL-2 (pM), tumor necrosis factor (TNF)-alpha (pg/mL), IL-6 (pg/mL), and IL-10 (pg/mL) were determined using enzyme immunoassay. We also analyzed the following immunologic tests: anti-nuclear antibodies (ANA), anti-mitochondrial antibodies (AMA), anti-parietal cell antibodies (PCA), anti-smooth muscle antibodies (SMA), anti-liver-kidney microsome antibodies type-1 (LKM-1), anti-Ro/SS-A, anti-La/SS-B, rheumatoid factor (RF), complement factors (C3 and C4), and cryoglobulins. RESULTS: Of the 20 patients with HCV-related SS, 18 were women and 2 men (mean age, 66 years). Patients with HCV-related SS had a different cytokine profile compared with patients with primary SS, with higher circulating levels of IL-6 (73.6 v 33.0 pg/mL, P =.045), IL-10 (6.7 v 3.1 pg/mL, P =.01), srIL-2 (124.6 v 72.7 pM, P =.001), and TNF-alpha (59.8 v 31.7 pg/mL, P =.003). The main immunologic features were ANA, detected in 75% of patients, RF in 63%, cryoglobulinemia in 50%, hypocomplementemia in 40%, SMA in 30%, PCA in 25%, anti-Ro/SS-A in 25%, AMA in 20% and anti-La/SS-B in 16%. When compared with primary SS patients, those with HCV-related SS had a higher prevalence of AMA (20% v 2%, P =.025), hypocomplementemia (40% v 11%, P =.015), and cryoglobulinemia (50% v 12%, P =.003). CONCLUSION: Although chronic HCV infection may mimic the main clinical, histologic and immunologic features of primary SS, patients with HCV-related SS showed some differentiated characteristics, including a predominant Th2 pattern and a higher frequency of cryoglobulinemia and hypocomplementemia (features closely related to HCV). This suggests that the SS observed in some HCV patients should be interpreted as one of the extrahepatic manifestations of chronic HCV infection.

Autoantibodies↗
PubMed1994

The role of humoral immunity in endometriosis.

In many ways endometriosis represents yet another form of unexplained infertility. The disease is clearly associated with a decrease in fecundity and while in advanced stages of the condition this infertility can be attributed to tubal factors, in mild stages of the disease the cause for the decrease in fertility is unknown. As in unexplained infertility, we have suggested that the impairment in fertility is due to autoantibody abnormalities. Endometriosis patients exhibit the same immunologic profile as previously described in women with unexplained infertility and repeated pregnancy loss. In fact, endometriosis is not only characterized by unexplained infertility but also by repeated and excessive pregnancy wastage. Its clinical presentation mimics that of an autoimmune disease, raising the question whether endometriosis is, in fact, an autoimmune disease. Endometriosis demonstrates immunologic abnormalities not only in respect to autoreactivity. Abnormalities in immune function have been widely reported in reference to almost any lymphocyte and macrophage function and, once again, the similarity to findings in patients with unexplained infertility is blatant. Abnormalities can be found in peripheral blood and especially prominently in peritoneal fluid. Treatment of immunologic abnormalities, and especially of autoantibody abnormalities, restores a level of fertility in endometriosis patients. It has also been demonstrated, in an animal model, that non-specific immune modulation may improve fertility.

Antibody Formation↗
PubMed1993

Abnormal (auto)immunity and endometriosis.

Immunologic abnormalities may precede endometriosis and be involved in its pathophysiology especially as it relates to the occurrence of infertility and pregnancy loss. Many cases of unexplained infertility may represent undiagnosed endometriosis. This is supported by the observation that immunologic profiles in endometriosis and unexplained infertility are very similar. It is argued that endometriosis is a systemic rather than local disease, thus requiring systemic therapy. Currently available medical and surgical techniques are effective in relieving symptomatology associated with endometriosis, although this is often temporary. A new clinical approach is needed that considers systemic presentation and likely immunologic pathophysiology.

Abortion, Spontaneous↗
PubMed1977

Immunological studies in onchocercosis patients.

The immunological profile of onchocercosis patients from an endemic region in Venezuela was studied. The sample was made up of patients suffering from onchocercosis and undergoing treatment, persons previously treated and apparently cured of the disease, and a group of apparently healthy individuals from the same area. The results obtained indicate that during the course of the disease the immunological apparatus suffers only slight modifications since no great variations were found in the immunoglobulin levels, the third component of the complement, the reactivity to DNCB, or the response of peripheral blood lymphocytes to mitogens. When under treatment, the levels of serum IgG and IgM are increased and there is a decrease in C3 levels. The slight modifications found can be attributed to the low severity of the disease as only one patient of those studied presented clinical manifestations ascribable to the disease (onchocercoma).

Adolescent↗
PubMed1993

[Microsurgical allotransplantation of fetal bone on a vascular peduncle: immunological aspects].

The authors studied the immunological profile of three patients after transplantation of bone allobrephotransplants with their microsurgical revascularization in the recipient zone. A reaction of rejection of the transplanted brephobone did not occur in any of the three cases. In transplantation of a complex brephobone the soft tissues overlying it, rejection of the soft tissues was encountered but there were no signs of bone rejection. The data of immunological monitoring correlate with the results of the clinicolaboratory and histological studies.

Bone Transplantation↗