Tag: HLA-DR

Persistence of circulating CD169+monocytes and HLA-DR downregulation underline the immune response impairment in PASC individuals: the potential contribution of different COVID-19 pandemic waves

Abstract:

The use of CD169 as a marker of viral infection has been widely discussed in the context of COVID-19, and in particular, its crucial role in the early detection of SARS-CoV-2 infection and its association with the severity and clinical outcome of COVID-19 were demonstrated. COVID-19 patients show relevant systemic alteration and immunological dysfunction that persists in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC).

It is critical to implement the characterization of the disease, focusing also on the possible impact of the different COVID-19 waves and the consequent effects found after infection. On this basis, we evaluated by flow cytometry the expression of CD169 and HLA-DR on monocytes from COVID-19 patients and PASC individuals to better elucidate their involvement in immunological dysfunction, also evaluating the possible impact of different pandemic waves.

The results confirm CD169 RMFI is a good marker of viral infection. Moreover, COVID-19 patients and PASC individuals showed high percentage of CD169+ monocytes, but low percentage of HLA-DR+ monocytes and the alteration of systemic inflammatory indices. We have also observed alterations of CD169 and HLA-DR expression and indices of inflammation upon different COVID-19 waves.

The persistence of specific myeloid subpopulations suggests a role of CD169+ monocytes and HLA-DR in COVID-19 disease and chronic post-infection inflammation, opening new opportunities to evaluate the impact of specific pandemic waves on the immune response impairment and systemic alterations with the perspective to provide new tools to monitoring new variants and diseases associated to emerging respiratory viruses.

Source: Fanelli M, Petrone V, Maracchioni C, Chirico R, Cipriani C, Coppola L, Malagnino V, Teti E, Sorace C, Zordan M, Vitale P, Iannetta M, Balestrieri E, Rasi G, Grelli S, Malergue F, Sarmati L, Minutolo A, Matteucci C. Persistence of circulating CD169+monocytes and HLA-DR downregulation underline the immune response impairment in PASC individuals: the potential contribution of different COVID-19 pandemic waves. Curr Res Microb Sci. 2023 Dec 12;6:100215. doi: 10.1016/j.crmicr.2023.100215. PMID: 38187999; PMCID: PMC10767315. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10767315/ (Full text)

Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto)immune, leaky gut, oxidative and nitrosative stress biomarkers

Abstract:

BACKGROUND: There is now evidence that specific subgroups of patients with Myalgic Encephalomyelitis / chronic fatigue syndrome (ME/CFS) suffer from a neuro-psychiatric-immune disorder. This study was carried out to delineate the expression of the activation markers CD38 and human leukocyte antigen (HLA) DR on CD4+ and CD8+ peripheral blood lymphocytes in ME/CFS.

METHODS: Proportions and absolute numbers of peripheral lymphocytes expressing CD3+, CD19+, CD4+, CD8+, CD38+ and HLA-DR+ were measured in ME/CFS (n=139), chronic fatigue (CF, n=65) and normal controls (n=40).

RESULTS: The proportions of CD3+, CD8+, CD8+CD38+ and CD8+HLA-DR+ were significantly higher in ME/CFS patients than controls, while CD38+, CD8+CD38+, CD8+HLA-DR+ and CD38+HLA-DR+ were significantly higher in ME/CFS than CF. The percentage of CD19+ cells and the CD4+/CD8+ ratio were significantly lower in ME/CFS and CF than in controls. There were highly significant inverse correlations between the increased expression of CD38+, especially that of CD8+CD38+, and the lowered CD4+/CD8+ ratio and CD19+ expression. There were no significant associations between the flow cytometric results and severity or duration of illness and peripheral blood biomarkers of oxidative and nitrosative stress (O&NS, i.e. IgM responses to O&N modified epitopes), leaky gut (IgM or IgA responses to LPS of gut commensal bacteria), cytokines (interleukin-1, tumor necrosis factor-α), neopterin, lysozyme and autoimmune responses to serotonin.

CONCLUSIONS: The results support that a) increased CD38 and HLA-DR expression on CD8+ T cells are biomarkers of ME/CFS; b) increased CD38 antigen expression may contribute to suppression of the CD4+/CD8+ ratio and CD19+ expression; c) there are different immune subgroups of ME/CFS patients, e.g. increased CD8+ activation marker expression versus inflammation or O&NS processes; and d) viral infections or reactivation may play a role in a some ME/CFS patients.

 

Source: Maes M, Bosmans E, Kubera M. Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto)immune, leaky gut, oxidative and nitrosative stress biomarkers. Neuro Endocrinol Lett. 2015;36(5):439-46. https://www.ncbi.nlm.nih.gov/pubmed/26707044

 

Immunity Impairment as a Result of Neurohormonal Disorders

Abstract:

An important principle of psychoneuroimmunologic interaction is that immunocytes act as if they were mobile sensitive organs for the central nervous system, producing local and systemic neuropeptides and immunological transmitters with appropriate stimulation. They inform the brain of local damage and mobilize the neuroendocrine system for protection. Their list is long and continues to grow. It includes: somatostatin, vasoactive intestinal peptide, thyroid stimulating hormone, human chorionic gonadotropin, follicle stimulating hormone, luteinizing hormone and other neurotransmitters and hormones, having immunomodulating properties.

This may indicate to close interaction between the immune and neuroendocrine systems, which may be involved into the disease process. A bright example of this may be a disease that has not been closely studied in our country, but is widespread throughout the world. This is the chronic fatigue syndrome, at the base of which lie disturbances of the central nervous, endocrine and immune systems. The idea that the chronic fatigue syndrome is a disturbance of the production of cytokines is related to a number of disturbances in the T system of immunity. It was found back in 1987-1988 that there is an increase in the level of HLA DR and IL-2 receptors and an increase in the ratio CD4/CD8 in patients suffering from this syndrome.

 

Source: Artsimovich NG, Galushina TS, Matvienko MA, Nastoyaschaya NN, Fadeeva TA, Shneidorova MA. Immunity Impairment as a Result of Neurohormonal Disorders. Russ J Immunol. 1999 Dec;4(4):343-345. http://www.ncbi.nlm.nih.gov/pubmed/12687153

 

A study of the immunology of the chronic fatigue syndrome: correlation of immunologic parameters to health dysfunction

Abstract:

Surface and intracellular immunologic and apoptotic markers and functional lymphocyte assays after stimulation with anti-CD3/anti-CD28 antibodies or phytohemagglutinin (PHA) were studied in 44 patients fulfilling the Oxford criteria for chronic fatigue syndrome (CFS). Results were then correlated to scores for the Short Form-36 health questionnaire (SF-36), which assesses eight aspects of patient’s well-being, and for the general health questionnaire (GHQ), which detects current psychiatric disorder.

Patients had significantly increased mean fluorescence intensity readings of HLA-DR in CD4 and CD8 cells (P < 0.05). Expression of the costimulatory receptor CD28 in CD8 cells was significantly reduced, and the apoptosis repressor ratio of bcl-2/bax in both CD4 and CD8 was increased in patients (P < 0.05).

Patients with increased HLA-DR expression had significantly lower SF-36 total scores, worse body pains, and poorer general health perception and physical functioning scores. Increased spontaneous lymphocyte proliferation was associated with poor general health perception. PHA proliferative responses were lower in patients with poor emotional and mental health scores, and the anti-CD3/anti-CD28 response was low in those with low general health perception scores.

Higher spontaneous proliferation and reduced PHA responses correlated with higher GHQ scores. Similarly, GHQ scores were significantly higher, indicating worse mental health, in those with lower total SF-36 scores and worse general and mental health scores in the SF-36 questionnaire.

Finally, higher expression of the costimulatory molecule CD28 correlated with higher total SF-36 scores, general health perception and social functioning scores, and with lower role limitation due to physical health. The increased expression of class II antigens and the reduced expression of the costimulatory receptor CD28, which is a marker of terminally differentiated cells, lend further support to the concept of immunoactivation of T-lymphocytes in CFS and may be consistent with the notion of a viral etiopathogenesis in the illness.

We report, for the first time, increased expression of the apoptosis repressor protein bcl-2, which may contribute to enhanced survival of activated lymphocytes. Using the SF-36 health assessment questionnaire and the GHQ, we demonstrated changes in different immunological parameters, each of which correlated with particular aspects of disease symptomatology.

 

Source: Hassan IS, Bannister BA, Akbar A, Weir W, Bofill M. A study of the immunology of the chronic fatigue syndrome: correlation of immunologic parameters to health dysfunction. Clin Immunol Immunopathol. 1998 Apr;87(1):60-7. http://www.ncbi.nlm.nih.gov/pubmed/9576011

 

Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome

Abstract:

Whether immunologic abnormalities correlate with fatigue severity and functional impairment in chronic fatigue syndrome (CFS) was investigated. Blood mononuclear cells were immunophenotyped and circulating ex vivo-produced cytokines were measured in 76 CFS patients and 69 healthy matched controls. Expression of CD11b on CD8 cells was significantly decreased in CFS patients. However, the previously reported increased expression of CD38 and HLA-DR was not confirmed. There was no obvious difference in apoptosis in leukocyte cultures, circulating cytokines, and ex vivo production of interleukin (IL)-1 alpha and IL-1 receptor antagonist. Endotoxin-stimulated ex vivo production of tumor necrosis factor-alpha and IL-beta was significantly lower in CFS. The immunologic test results did not correlate with fatigue severity or psychologic well-being was measured by Checklist Individual Strength, Beck Depression Inventory, and Sickness Impact Profile. Thus, these immunologic tests cannot be used as diagnostic tools in individual CFS patients.

 

Source: Swanink CM, Vercoulen JH, Galama JM, Roos MT, Meyaard L, van der Ven-Jongekrijg J, de Nijs R, Bleijenberg G, Fennis JF, Miedema F, van der Meer JW. Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome. J Infect Dis. 1996 Feb;173(2):460-3. http://jid.oxfordjournals.org/content/173/2/460.long (Full article)

 

Chronic fatigue syndrome. Immunological findings vary between populations

Comment on: Longitudinal study of outcome of chronic fatigue syndrome. [BMJ. 1994]

 

Editor,-We were interested in Andrew Wilson and colleagues’ paper investigating predictors of the long term outcome of the chronic fatigue syndrome in patients in Australia. We have investigated the association between immune activation and presumed cutaneous anergy in 68 Scottish patients with the syndrome (19 cases conformed to the Centers for Disease Control’s criteria, 18 cases had been diagnosed by a consultant, 28 cases had been diagnosed by a general practitioner, and three patients referred themselves) and 22 family contacts. We assessed delayed hypersensitivity responses (using Multitest antigens and tuberculin skin tests) and evaluated peripheral blood activation markers (CD8, CD38/ CD llb/HLA-DR) using flow cytometry. Patients were classified into three groups on the basis of current severity of illness and mobility.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2540184/pdf/bmj00440-0055b.pdf

 

Source: Abbot NC, Spence VA, Lowe JG, Potts RC, Hassan AH, Belch JJ, Beck JS. Chronic fatigue syndrome. Immunological findings vary between populations. BMJ. 1994 May 14;308(6939):1299. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2540184/

 

Immunologic abnormalities associated with chronic fatigue syndrome

Abstract:

Several aspects of cellular immunity in patients with clinically defined chronic fatigue syndrome (CFS) were evaluated and compared with those in healthy individuals.

Flow cytometric analyses revealed normal expression of total T (CD3+), B (CD19+), and NK (natural killer) (CD16+, CD56+) markers on the surface of peripheral blood mononuclear cells (PMC) from patients with CFS.

However, compared with those of healthy individuals, patients’ CD8+ T cells expressed reduced levels of CD11b and expressed the activation markers CD38 and HLA-DR at elevated levels. In many of the individuals in whom expression of CD11b was reduced the expression of CD28 was increased.

These findings indicate expansion of a population of activated CD8+ cytotoxic T lymphocytes. A marked decrease in NK cell activity was found in almost all patients with CFS, as compared with that in healthy individuals. No substantial abnormalities in monocyte activity or T cell proliferation were observed. The results of this study suggest that immune cell phenotype changes and NK cell dysfunction are common manifestations of CFS.

 

Source: Barker E, Fujimura SF, Fadem MB, Landay AL, Levy JA. Immunologic abnormalities associated with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S136-41. http://www.ncbi.nlm.nih.gov/pubmed/8148441

 

Chronic fatigue syndrome: clinical condition associated with immune activation

Abstract:

There is much conflicting immunological and viral data about the causes of chronic fatigue syndrome (CFS); some findings support the notion that CFS may be due to one or more immune disorders that have resulted from exposure to an infectious agent.

In the present study, flow cytometry and several different recognising T, B, and natural killer (NK) cell populations as well as activation and cell adhesion antigens were used to study 147 individuals with CFS.

Compared with healthy controls, a reduced CD8 suppressor cell population and increased activation markers (CD38, HLA-DR) on CD8 cells were found. The differences were significant (p = 0.01) in patient with major symptoms of the disease. These immunological indices were not observed in 80 healthy individuals, in 22 contacts of CFS patients, or in 43 patients with other diseases.

No correlation of these findings in CFS patients with any known human viruses could be detected by serology. The findings suggest that immune activation is associated with many cases of CFS.

 

Source: Landay AL, Jessop C, Lennette ET, Levy JA. Chronic fatigue syndrome: clinical condition associated with . Lancet. 1991 Sep 21;338(8769):707-12. http://www.ncbi.nlm.nih.gov/pubmed/1679864