Current Knowledge about Nonclassical Monocytes in Patients with Multiple Sclerosis, a Systematic Review.

Monocytes play a critical role in the initiation and progression of multiple sclerosis (MS). Recent research indicates the importance of considering the roles of monocytes in the management of MS and the development of effective interventions. This systematic review examined published research on the roles of nonclassical monocytes in MS and how they influence disease management. Reputable databases, such as PubMed, EMBASE, Cochrane, and Google Scholar, were searched for relevant studies on the influence of monocytes on MS. The search focused on studies on humans and patients with experimental autoimmune encephalomyelitis (EAE) published between 2014 and 2024 to provide insights into the study topic. Fourteen articles that examined the role of monocytes in MS were identified; the findings reported in these articles revealed that nonclassical monocytes could act as MS biomarkers, aid in the development of therapeutic interventions, reveal disease pathology, and improve approaches for monitoring disease progression. This review provides support for the consideration of monocytes when researching effective diagnostics, therapeutic interventions, and procedures for managing MS pathophysiology. These findings may guide future research aimed at gaining further insights into the role of monocytes in MS.

Acute orchitis deciphered: Coxsackievirus B strains are the main etiology and their presence in semen is associated with acute inflammation and risk of persistent oligozoospermia.

Although various viruses are considered to be the clinical cause for acute orchitis, it is completely unclear to what extent and which viruses are etiologically involved in acute orchitis and what the clinic and course of these patients are like. Therefore, a prospective study was set up to decipher acute isolated orchitis. Between July 2007 and February 2023, a total of 26 patients with isolated orchitis were recruited and compared with 530 patients with acute epididymitis. We were able to show for isolated orchitis, that (1) orchitis is usually of viral origin (20/26, 77%) and enteroviruses with coxsackievirus B strains (16/26, 62%) are predominant, (2) virus isolates could be received from semen indicating the presence of replication-competent virus particles, (3) a polymerase chain reaction (PCR) for enteroviruses should be conducted using semen provided at the onset of disease, because the virus is not detectable in serum/urine, (4) there is a circannual occurrence with the maximum in summer, (5) orchitis is associated with a characteristic inflammatory cytokine panel in the semen and systemic inflammation, (6) orchitis is usually rapidly self-limiting, and (7) about 30% of patients (6/20) suffer ongoing oligozoospermia. These seven emerging aspects are likely to fundamentally change thinking and clinical practice regarding acute isolated orchitis.

Comparison of Urine Flow Cytometry on the UF-1000i System and Urine Culture of Urine Samples from Urological Patients.

INTRODUCTION: The aims of this study were to evaluate urine flow cytometry (UFC) as a tool to screen urine samples of urological patients for bacteriuria and to compare UFC and dipstick analysis with urine culture in a patient cohort at a urological department of a university hospital. METHODS AND MATERIAL: We screened 662 urine samples from urological patients (75.2% male; 80.7% inpatients; mean age 58 years). UFC results were compared to microbiological urine culture. RESULTS: The accuracy in using the UFC-based parameters for detecting cultural bacteriuria was 91.99% and 88.97% for ≥105 colony-forming units (CFU)/mL and ≥104 CFU/mL, respectively. UFC and leukocyte dipstick analysis measured leukocyturia similarly (Pearson correlation coefficient 0.87, p value <0.01%), but dipstick analysis scored less accurately on bacteriuria (accuracy 59.37% and 62.69%). UFC remained effective in subgroup analysis of patients of both sexes and with different urological conditions with its overall use only slightly impaired when assessing gross hematuria (NPV 84.62% for ≥104 CFU/mL). UFC also reliably removed those urine samples below cutoffs with negative predictive values of 99.28% for ≥105 CFU/mL and 95.86% for ≥104 CFU/mL. CONCLUSION: Counting bacteria with UFC is an accurate and rapid method to determine significant bacteriuria in urological patients and is superior to dipstick analysis or indirect surrogate parameters such as leukocyturia. When UFC is available, we recommend it to be used for the diagnosis of bacteriuria over findings obtained by dipstick analysis.

Experimental laboratory biomarkers in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system; the cause of this condition remains unknown. Researchers have analyzed different biomarkers related to MS. Here, experimental laboratory biomarkers for MS are identified and analyzed. METHODS: The current study examined articles investigating biomarkers for MS. Records were obtained from the PubMed, LILACS, and EBSCO databases using an identical search strategy and terms that included "multiple sclerosis," "MS," and "biomarkers." In the current review, we also focus on lesser known biomarkers that have not yet been established for use in clinical practice. RESULTS: Previous studies have explored molecular substances that may help diagnose MS and manage its adverse effects. Commonly studied factors include neurofilaments, sCD163, CXCL13, NEO, NF­L, OPN, B cells, T cells, and integrin-binding proteins. CONCLUSIONS: Interactions between environmental and genetic factors have been implicated in the development of MS. Previous investigations have identified a wide range of biomarkers that can be used for diagnosis and disease management. These molecules and their associated studies provide vital insight and data to help primary physicians improve clinical and health outcomes for MS patients.

The Use of Kappa Free Light Chains to Diagnose Multiple Sclerosis.

Background: The positive implications of using free light chains in diagnosing multiple sclerosis have increasingly gained considerable interest in medical research and the scientific community. It is often presumed that free light chains, particularly kappa and lambda free light chains, are of practical use and are associated with a higher probability of obtaining positive results compared to oligoclonal bands. The primary purpose of the current paper was to conduct a systematic review to assess the up-to-date methods for diagnosing multiple sclerosis using kappa and lambda free light chains. Method: An organized literature search was performed across four electronic sources, including Google Scholar, Web of Science, Embase, and MEDLINE. The sources analyzed in this systematic review and meta-analysis comprise randomized clinical trials, prospective cohort studies, retrospective studies, controlled clinical trials, and systematic reviews. Results: The review contains 116 reports that includes 1204 participants. The final selection includes a vast array of preexisting literature concerning the study topic: 35 randomized clinical trials, 21 prospective cohort studies, 19 retrospective studies, 22 controlled clinical trials, and 13 systematic reviews. Discussion: The incorporated literature sources provided integral insights into the benefits of free light chain diagnostics for multiple sclerosis. It was also evident that the use of free light chains in the diagnosis of clinically isolated syndrome (CIS) and multiple sclerosis is relatively fast and inexpensive in comparison to other conventional state-of-the-art diagnostic methods, e.g., using oligoclonal bands (OCBs).

Neutrophil Extracellular Traps (NETs) and Vasculitis.

Background: Neutrophil extracellular traps (NETs) have been implicated in host immune responses. Attempts have been made to examine how NETs affect the pathogenesis of complications such as autoimmune and vascular disorders. Aim: This study aimed to explore the relationship between NETs and vasculitis. Material and Methods: The current study entailed the searching of PsycINFO, PubMed, Web of Science, and CINAHL for articles related to the research topic. The search terms and phrases included "vasculitis," "NETs," "neutrophil extracellular traps," "NETosis," and "pathogenesis." The search was limited to articles published between 2009 and 2019. Results: Researchers have shown that NETs contribute to the pathogenesis of vasculitis through different mechanisms and processes, including renal failure and vascular damage. The protective effects of NETs have also been highlighted. Discussion: Overall, some scholars have shown the effectiveness of using DNase I and the PAD4 inhibitor Cl-amidine to treat vasculitis by restricting NET formation. However, observations have been noted in only animal experimental models. Conclusion: Neutrophil hyperactivity and its role in vasculitis are not yet fully understood. More studies aiming to determine the accurate function of NETs in vasculitis pathogenesis, particularly in humans, should be undertaken. Intensive research on NETs and vasculitis can increase the knowledge of medical practitioners and contribute to the development of new treatment methods to enhance patient outcomes in the future.

Influence of Left Atrial Appendage Amputation on Natriuretic Peptides-A Randomized Controlled Trial.

BACKGROUND: Closure or amputation of the left atrial appendage (LAA) is a common therapy for atrial fibrillation (AF). As the LAA is a hormone-producing organ, however, amputation is still somewhat controversial. We examined patients after surgical AF therapy with or without LAA amputation to determine the influence of LAA amputation on pro-atrial natriuretic peptide (proANP) and B-type natriuretic peptide (BNP) plasma levels and on clinical severity of heart failure. METHODS: Twenty-one consecutive patients were prospectively randomized to either undergo LAA amputation (n = 10) or no LAA amputation (n = 11) between 05/2015 and 10/2015. All patients underwent coronary and/or valve surgery and concomitant AF surgery with either cryoablation (n = 3) or radio frequency ablation (n = 17). ProANP and BNP levels were measured preoperatively and until 800 days postoperatively. RESULTS: Baseline proANP values were comparable between the groups (without LAA amputation: 4.2 ± 2.1 nmol/L, with LAA amputation: 5.6 ± 3.6 nmol/L). Postoperatively, proANP levels rose markedly in both groups. Even after LAA amputation, proANP levels remained elevated for 7 days postoperatively but fell to baseline levels at day 31 and remained on baseline level at 800 days postoperatively. ProANP levels in the LAA amputation group (5.8-9.7 nmol/L) were not significantly lower than in the group without LAA amputation (9.2-14.1 nmol/L; p = 0.357). BNP levels also rose after surgery in both groups until day 7. At 800 days after surgery, BNP levels were back at baseline levels in both groups. Clinical follow-up at 2 years postoperatively showed no difference in heart failure symptoms or need for heart failure medication between the groups. CONCLUSION: In contrast to commonly held beliefs about the endocrine and reservoir functions of the LAA, there seems to be no clinically relevant detrimental effect of LAA amputation on natriuretic peptide levels and severity of heart failure until up to 2 years postoperatively.

Refractory neutrophil activation in type 2 diabetics with chronic periodontitis.

BACKGROUND: Inflammation increases diabetes mellitus type 2 (T2DM) progression and severity. T2DM patients are at high risk of the rapid development of chronic periodontitis (CP). Topical presence, high numbers, and bactericidal effects of immune cells are challenged by augmented antigen-induced inflammation, which promotes both diseases. OBJECTIVES: To investigate gingival cellular inflammatory responses in individuals with previously undiagnosed T2DM with CP or CP alone and in systemically and periodontally healthy controls (H) in vivo and to establish an ex vivo technique permitting quantitative and qualitative assessments of gingival crevicular immune cells. MATERIALS AND METHODS: T2DM + CP, CP, and H individuals (n = 10, each) received a 2-week oral hygiene regimen (OHR). Afterwards, a noninvasive sampling technique was performed to evaluate gingival inflammation induced under standardized conditions in vivo, that is, in the absence of severe periodontal destruction and inflammation at clinically healthy sites. Stimuli (casein/test or phosphate-buffered saline w/o. Ca2+ or Mg2+ , PBS(-/-) /control) were randomly applied contralaterally in the gingival sulci of participants' upper dentes canini. One day after completion of the OHR, gingival crevicular fluid (GCF) was kinetically assayed between the time of the baseline (BL) measurement and 55 minutes. Polymorphonuclear leukocyte (PMN) content (PMNGCF ) was quantitated at an optimum time of 35 minutes. PMNGCF counts reflect local inflammation. Ex vivo samples were fluorimetrically labeled, gated according to the donor's peripheral blood polymorphonuclear neutrophils (PMNPB ), and then counted, employing flow cytometry. RESULTS: PMNGCF counts in unstimulated gingival crevices (at BL) in the T2DM + CP group were higher than those in the CP and H groups. PMNGCF counts were elevated in casein vs PBS(-/-) -stimulated gingival crevices in all groups. Patients with T2DM + CP showed increased PMNGCF counts compared to those with CP (P = .035) according to scatter plots. CD45+ counts in the stimulated sites in T2DM + CP patients were higher than those in CP and H patients (P = .041). Under stimulation conditions, the CD45+ counts differed from those under placebo conditions (P = .019), indicating augmented, inducible inflammatory leukocyte infiltrate in T2DM + CP patients. CONCLUSIONS: This noninvasive technique permits quantitative assessment of (experimental) gingival inflammation in vivo, revealing an influence of T2DM + CP on the number of primary immune cells in the gingival crevice. Patients who are challenged with (local) leukocytosis are likely at risk of collateral damage to the gingival crevice neighboring tissues, favoring the severity and progression of CP and consequently T2DM (www.clinicaltrials.gov NCT01848379).

Predicting Cardiac Surgery-Associated Acute Kidney Injury Using a Combination of Clinical Risk Scores and Urinary Biomarkers.

BACKGROUND: Prediction, early diagnosis, and therapy of cardiac surgery-associated acute kidney injury (CSA-AKI) are challenging. We prospectively tested a staged approach to identify patients at high risk for CSA-AKI combining clinical risk stratification and early postoperative quantification of urinary biomarkers for AKI. METHODS: All patients, excluding those on chronic hemodialysis, undergoing scheduled surgery with cardiopulmonary bypass between August 2015 and July 2016 were included. First, patients were stratified by calculating the Cleveland clinic score (CCS) and the Leicester score (LS). In high-risk patients (defined as LS > 25 or CCS > 6), urinary concentrations of biomarkers for AKI ([TIMP-2]*[IGFBP-7]) were evaluated 4 hours postoperatively. CSA-AKI was observed until postoperative day 6 and classified using the Kidney Disease: Improving Global Outcomes criteria. RESULTS: AKI occurred in 352 of613 patients (54%). In high-risk patients, AKI occurred more frequently than in low-risk patients (66 vs. 49%; p = 0.001). In-hospital mortality after AKI stage 2 (15%) or AKI stage 3 (49%) compared with patients without AKI (1.8%; p = 0.001) was increased. LS was predictive for all stages of AKI (area under the curve [AUC] 0.601; p < 0.001) with a poor or fair accuracy, while CCS was only predictive for stage 2 or 3 AKI (AUC 0.669; p < 0.001) with fair accuracy. In 133 high-risk patients, urinary [TIMP-2]*[IGFBP-7] was significantly predictive for all-stage AKI within 24 hours postoperatively (AUC 0.63; p = 0.017). However, for the majority of AKI (55%), which occurred beyond 24 hours postoperatively, urinary [TIMP-2]*[IGFBP-7] was not significantly predictive. Sensitivity for all-stage AKI within 24 hours was 0.38 and specificity was 0.81 using a cutoff value of 0.3. CONCLUSION: CSA-AKI is a relevant and frequent complication after cardiac surgery. Patients at high risk for CSA-AKI can be identified using clinical prediction scores, however, with only poor to fair accuracy. Due to its weak test performance, urinary [TIMP-2]*[IGFBP-7] quantification 4 hours postoperatively does not add to the predictive value of clinical scores.

Impact of B cells to the pathophysiology of multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a chronic autoimmune disorder that affects the central nervous system and compromises the health and well-being of millions of people worldwide. B cells have been linked to MS and its progression. This review aimed to determine the role of B cells in MS development. METHODS: Articles used in this review were obtained from PubMed, LILACS, and EBSCO. The search terms and phrases included "multiple sclerosis," "MS," "B-Cells," "pathogenesis," and "development." Original research studies and articles on MS and B cells published between 2007 and 2018 were included. RESULTS: Results from the selected articles showed a significant connection between B cell groups and MS. B cells act as a significant source of plasma cells, which generate antibodies while also regulating autoimmune processes and T cell production. In addition, B cells regulate the release of molecules that affect the proinflammatory actions of other immune cells. DISCUSSION: B cells play key roles in immune system functioning and MS. The findings of this review illustrate the complex nature of B cell actions, their effects on the autoimmune system, and the method by which they contribute to MS pathogenesis. CONCLUSION: Previous research implicates biological, genetic, and environmental factors in MS pathogenesis. This review suggests that B cells contribute to MS development and advancement by influencing and regulating autoimmune processes such as T cell production and APC activity.

Coevolution of the coagulation and immune systems.

BACKGROUND: Higher organisms rely on the coagulation and immune systems to fight disease-causing pathogens and other foreign invaders in the body. Coagulation has an important role as a barrier against foreign bodies, including bacteria, viruses, and protozoa. The protective responses associated with the coagulation and immune systems can protect the host organism from a wide range of pathogens, such as viruses, parasites, fungi, and even bacteria. AIM: The purpose of this paper was to review available research on the evolution of the coagulation and immune systems. MATERIALS AND METHODS: The study analyzed evidence from studies that have examined the coagulation and immune systems in the context of evolutionary processes. The articles used in the review were identified from the PsycINFO, CIHAHL, PubMed, Web of Science, and CIHAHL databases. RESULTS: Studies have shown that both the coagulation system and the early immune system originated from the same initial system in early organisms. Some researchers argue that hemocytes from lower organisms are the common link from which the immune system and coagulation system developed. DISCUSSION AND CONCLUSION: Simple organisms have hemocytes that can carry out both immune response and coagulation processes. Evolution led to the separation of these processes in higher organisms. Furthermore, this divergence resulted in the emergence of thrombocytes and plasmatic coagulation subsystems. These observations explain why there is some form of overlap between immunity and hemostasis, even in advanced organisms such as vertebrates. Several phenomena in clinical medicine related to coagulation and immunity can be explained by this overlap and are consistent with the hypothesis of the coevolution of coagulation and the immune system.

Metabolomics of Type 1 and Type 2 Diabetes.

Type 1 and type 2 diabetes mellitus (DM) are chronic diseases that affect nearly 425 million people worldwide, leading to poor health outcomes and high health care costs. High-throughput metabolomics screening can provide vital insight into the pathophysiological pathways of DM and help in managing its effects. The primary aim of this study was to contribute to the understanding and management of DM by providing reliable evidence of the relationships between metabolites and type 1 diabetes (T1D) and metabolites and type 2 diabetes (T2D). Information for the study was obtained from the PubMed, MEDLINE, and EMBASE databases, and leads to additional articles that were obtained from the reference lists of the studies examined. The results from the selected studies were used to assess the relationships between diabetes (T1D and/or T2D) and metabolite markers-such as glutamine, glycine, and aromatic amino acids-in patients. Seventy studies were selected from the three databases and from the reference lists in the records retrieved. All studies explored associations between various metabolites and T1D or T2D. This review identified several plasma metabolites associated with T2D prediabetes and/or T1D and/or T2D in humans. The evidence shows that metabolites such as glucose, fructose, amino acids, and lipids are typically altered in individuals with T1D and T2D. These metabolites exhibit significant predictive associations with T2D prediabetes, T1D, and/or T2D. The current review suggests that changes in plasma metabolites can be identified by metabolomic techniques and used to identify and analyze T1D and T2D biomarkers. The results of the metabolomic studies can be used to help create effective interventions for managing these diseases.

Tumor Microenvironment.

BACKGROUND AND OBJECTIVES: The tumor microenvironment has been widely implicated in tumorigenesis because it harbors tumor cells that interact with surrounding cells through the circulatory and lymphatic systems to influence the development and progression of cancer. In addition, nonmalignant cells in the tumor microenvironment play critical roles in all the stages of carcinogenesis by stimulating and facilitating uncontrolled cell proliferation. AIM: This study aims to explore the concept of the tumor microenvironment by conducting a critical review of previous studies on the topic. Materials and Methods: This review relies on evidence presented in previous studies related to the topic. The articles included in this review were obtained from different medical and health databases. RESULTS AND DISCUSSION: The tumor microenvironment has received significant attention in the cancer literature, with a particular focus on its role in tumor development and progression. Previous studies have identified various components of the tumor microenvironment that influence malignant behavior and progression. In addition to malignant cells, adipocytes, fibroblasts, tumor vasculature, lymphocytes, dendritic cells, and cancer-associated fibroblasts are present in the tumor microenvironment. Each of these cell types has unique immunological capabilities that determine whether the tumor will survive and affect neighboring cells. CONCLUSION: The tumor microenvironment harbors cancer stem cells and other molecules that contribute to tumor development and progression. Consequently, targeting and manipulating the cells and factors in the tumor microenvironment during cancer treatment can help control malignancies and achieve positive health outcomes.

Update on the types and usage of liquid biopsies in the clinical setting: a systematic review.

BACKGROUND: This systematic review aimed to gather evidence from research on the current state of liquid biopsy in medical practice, specifically focusing on mutation detection and monitoring. METHODS: A systematic search was performed via Medline. RESULTS: The results of this investigation indicate that liquid biopsy plays a critical role in the detection and management of tumors. This technique gives healthcare providers the ability to gather critical and reliable information that may potentially shape the diagnosis, treatment, and prognosis of a variety of cancers in the near future. This study further reveals that liquid biopsy has several potential shortcomings that may limit its application and use in the healthcare setting. Nevertheless, liquid biopsy remains a valuable tool that is gradually becoming a part of routine healthcare practice in oncology departments and hospitals worldwide. CONCLUSIONS: The evidence described herein reveals the potential relevance of liquid biopsy as an important prognostic, diagnostic, and theranostic tool. This non-invasive procedure enables healthcare practitioners to detect and monitor genomic alterations and will likely replace tumor tissue biopsy as the standard method for detecting and monitoring mutations in the future. The information obtained herein can enable physicians to make informed decisions regarding current treatment options; however, liquid biopsy has not yet been incorporated into routine clinical diagnostics for cancer patients.

Gut-brain axis biochemical signalling from the gastrointestinal tract to the central nervous system: gut dysbiosis and altered brain function.

BACKGROUND: The gut-brain axis facilitates a critical bidirectional link and communication between the brain and the gut. Recent studies have highlighted the significance of interactions in the gut-brain axis, with a particular focus on intestinal functions, the nervous system and the brain. Furthermore, researchers have examined the effects of the gut microbiome on mental health and psychiatric well-being.The present study reviewed published evidence to explore the concept of the gut-brain axis. AIMS: This systematic review investigated the relationship between human brain function and the gut-brain axis. METHODS: To achieve these objectives, peer-reviewed articles on the gut-brain axis were identified in various electronic databases, including PubMed, MEDLINE, CIHAHL, Web of Science and PsycINFO. RESULTS: Data obtained from previous studies showed that the gut-brain axis links various peripheral intestinal functions to brain centres through a broad range of processes and pathways, such as endocrine signalling and immune system activation. Researchers have found that the vagus nerve drives bidirectional communication between the various systems in the gut-brain axis. In humans, the signals are transmitted from the liminal environment to the central nervous system. CONCLUSIONS: The communication that occurs in the gut-brain axis can alter brain function and trigger various psychiatric conditions, such as schizophrenia and depression. Thus, elucidation of the gut-brain axis is critical for the management of certain psychiatric and mental disorders.

Error analysis in newborn screening: can quotients support the absolute values?

Newborn screening is performed using modern tandem mass spectrometry, which can simultaneously detect a variety of analytes, including several amino acids and fatty acids. Tandem mass spectrometry measures the diagnostic parameters as absolute concentrations and produces fragments which are used as markers of specific substances. Several prominent quotients can also be derived, which are quotients of two absolute measured concentrations. In this study, we determined the precision of both the absolute concentrations and the derived quotients. First, the measurement error of the absolute concentrations and the measurement error of the ratios were practically determined. Then, the Gaussian theory of error calculation was used. Finally, these errors were compared with one another. The practical analytical accuracies of the quotients were significantly higher (e.g., coefficient of variation (CV) = 5.1% for the phenylalanine to tyrosine (Phe/Tyr) quotient and CV = 5.6% for the Fisher quotient) than the accuracies of the absolute measured concentrations (mean CVs = 12%). According to our results, the ratios are analytically correct and, from an analytical point of view, can support the absolute values in finding the correct diagnosis.

Multiple Sclerosis and Schizophrenia.

The psychiatric and neurological aspects of health may present methodological challenges in the diagnosis and treatment of disease. This is especially true for patients whose symptoms indicate the coexistence of multiple sclerosis (MS) and schizophrenia (SCZ). These cases raise critical questions regarding the relationship between the mind and the brain. Studies have noted that patients with MS have an increased risk of developing SCZ or bipolar disorder (BD). It is suggested here that MS and a subgroup of SCZ have similar etiologies. Factors such as gender, ethnicity, geography and season also have an influence on the occurrence of MS and SCZ. This paper aims to examine the differences and similarities between SCZ and MS. For this purpose, scientific papers examining various factors associated with these disorders were reviewed, and similarities and differences in genetic, immunological, seasonal, geographical, and gender-related risk factors and limited similarities in ethnic factors between the two diseases were identified. The findings suggest that subgroups of these two diseases may belong to the same class of disorders.

Early activation of CD4+ and CD8+ T lymphocytes by myelin basic protein in subjects with MS.

BACKGROUND: Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. In this study, whole blood samples were analyzed for activation capacity and the activatability of CD4+ and CD8+ T-lymphocytes by human total myelin basic protein (MBP), human MBP 104-118 fragment, and guinea pig MBP 68-82 fragment. METHODS: Whole blood samples from healthy human subjects were compared with samples from patients with multiple sclerosis (MS). In particular, the expression of CD69, a surface marker of T-lymphocyte activity, was measured via flow cytometry before and after 14 h of incubation with human total MBP, MBP 104-118 fragment and/or guinea pig MBP 68-82 fragment. The results were compared between 15 patients with MS and 15 healthy subjects. RESULTS: In response to all three MBP forms, CD4+ and CD8+ T-lymphocytes from patients with MS demonstrated greater activatability than those from healthy subjects. These results indicate that in patients with MS, latent pre-activation to MBP epitopes results in an increased activation capacity of T-lymphocytes. CONCLUSION: This effect may occur because immunization against MBP (at least in a subset of patients) plays a pathophysiological role in MS pathogenesis. Alternatively, this result may represent a non-specific, bystander autoimmune phenomenon.