Changes in natural killer cell phenotype in patients with post-viral fatigue syndrome

Abstract:

We analysed peripheral blood CD56+ natural killer (NK) cell subsets in 23 carefully characterized patients with post-viral fatigue syndrome (PFS), compared with 19 healthy controls, using fluorochrome-conjugated, specific monoclonal antibodies and the FACScan.

We found significantly increased percentages of CD56+, and especially CD56bright+ NK cells in PFS patients. We also found significantly increased percentages of CD56+ high affinity interleukin-2 (IL-2) receptor (CD25)+ and CD56+ transferrin receptor (CD71+) subsets of cells, most of which also stained brightly for CD56.

Also, we found an increased percentage of CD56+ CD3+ cells, many of which stained brightly for CD56, although there was no increase in the percentage of CD56- CD3+ T cells in these patients. These observations, in conjunction with very low percentage of CD56- CD25+ cells, suggest that there is a preferential involvement of this minor subset of CD56+ CD3+ T cells in PFS.

Finally, a decreased percentage of CD56+ Fc gamma receptor (CD16)+ NK cells was identified, which suggests a reduced capacity of antibody-dependent cellular cytotoxicity in PFS patients. Subsets of CD56+ NK cells co-expressing CD2, CD4 or CD8 did not show any significant difference between PFS patients and healthy controls.

These phenotypic changes provide laboratory evidence of immunological abnormalities in this syndrome, and, we suggest, may be consistent with persistent viral infection.

 

Source: Morrison LJ, Behan WH, Behan PO. Changes in natural killer cell phenotype in patients with post-viral fatigue syndrome. Clin Exp Immunol. 1991 Mar;83(3):441-6. http://www.ncbi.nlm.nih.gov/pubmed/1706238

You can read the full article herehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1535328/

 

Natural killer cells and the post viral fatigue syndrome

Abstract:

60 patients were referred with a diagnosis of post viral fatigue syndrome (PVFS), but only 50 fulfilled strict criteria for this illness. Many lymphocyte subpopulations were normal, but there was a spectrum of natural killer (NK) cell results: 20/50 (40%) were raised; 8/50 (16%) were low;, 5/50 (10%) were low initially but normal on repeat testing; 17/50 (34%) were normal.

When patients were categorised on their NK cell results, there were significant differences in the two groups with raised or low NK cells compared to the “Not PVFS” group: the CD8 cells were increased (p less than 0.001, p less than 0.02) and the CD4/CD8 ratio was reduced (p less than 0.05) but the CD4 cells were normal.

Clinical data showed that the “Not PVFS” group were older, with less severe illness, less muscle pain and less virological evidence of infection. It is postulated that patients have low NK cells initially and then progress to normal or raised levels dependent on factors such as stress, other infections and behaviour.

 

Source: Ho-Yen DO, Billington RW, Urquhart J. Natural killer cells and the post viral fatigue syndrome. Scand J Infect Dis. 1991;23(6):711-6. http://www.ncbi.nlm.nih.gov/pubmed/1815333

 

Immunologic abnormalities in chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS), formerly known as chronic Epstein-Barr virus syndrome, is a clinical state of some complexity and uncertain etiology. In order to characterize in a comprehensive manner the status of laboratory markers associated with cellular immune function in patients with this syndrome, 30 patients with clinically defined CFS were studied.

All of the subjects were found to have multiple abnormalities in these markers. The most consistent immunological abnormality detected among these patients, when compared with normal controls, was low natural killer (NK) cell cytotoxicity. The number of NK cells, as defined by reactivity with monoclonal antibody NKH.1 (CD56), was elevated, but the killing of K562 tumor cells per CD56 cell was significantly diminished.

Lymphoproliferative responses after stimulation with phytohemagglutinin and pokeweed mitogen were decreased in most patients when compared with those in normal controls, as was the production of gamma interferon following mitogen stimulation. Lymphocyte phenotypic marker analysis of peripheral blood lymphocytes showed that there were significant differences between patients with CFS and controls.

There was an increase in the percentage of suppressor-cytotoxic T lymphocytes, CD8, and a proportionally larger increase in the number of CD8 cells expressing the class II activation marker. Most patients had an elevated number of CD2 cells which expressed the activation marker CDw26. The numbers of CD4 cells and the helper subset of CD4+CD29+ cells in patients with CFS were not different from those in controls. There was, however, a significant decrease in the suppressor inducer subset of CD4+ CD45RA+ cells. The number of B cells, CD20 and CD21, were elevated, as were the numbers of a subset of B cells which coexpressed CD20 and CD5.

The patterns of immune marker abnormalities observed was compatible with a chronic viral reactivation syndrome.

 

Source: Klimas NG, Salvato FR, Morgan R, Fletcher MA. Immunologic abnormalities in chronic fatigue syndrome. J Clin Microbiol. 1990 Jun;28(6):1403-10. http://www.ncbi.nlm.nih.gov/pubmed/2166084

Note: You can read the full article herehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC267940/

 

The chronic fatigue syndrome: definition, current studies and lessons for fibromyalgia research

Abstract:

Chronic fatigue syndrome (CFS) is characterized by chronic, debilitating fatigue lasting greater than 6 months. Frequent chronic and recurrent findings include fever, pharyngitis, myalgias, adenopathy, arthralgias, difficulties in cognition and disorders of mood. In the majority of patients, the illness starts suddenly with an acute, “flu-like” illness.

The following laboratory abnormalities are seen with some frequency, although none are seen in all patients: lymphocytosis, atypical lymphocytosis, monocytosis, elevation of hepatocellular enzymes, low levels of antinuclear antibodies, varying levels of antithyroid antibodies, partial hypergammaglobulinemia, elevated CD4:CD8 ratio, decreased cytolytic activity of natural killer cells, and low levels of immune complexes. Clinical and serologic studies suggest an association of CFS with all of the human herpesviruses, particularly Epstein-Barr virus (EBV) and the recently discovered human B lymphotropic virus (HBLV) or human herpesvirus 6; neither EBV nor HBLV has yet been shown to play a causal role in the illness.

Preliminary evidence suggests that many of these features of CFS also are seen in patients with fibromyalgia.

 

Source: Komaroff AL, Goldenberg D. The chronic fatigue syndrome: definition, current studies and lessons for fibromyalgia research. J Rheumatol Suppl. 1989 Nov;19:23-7. http://www.ncbi.nlm.nih.gov/pubmed/2691680

 

Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome

Abstract:

Natural killer (NK)3 cells are large granular lymphocytes that appear to play a significant role in the host’s defense against viral infection. We performed an extensive phenotypic and functional characterization of NK cells on 41 patients with the chronic fatigue syndrome (CFS), or “chronic active Epstein-Barr virus infection” syndrome, and on 23 age- and sex-matched asymptomatic control subjects in an attempt to further characterize this illness.

These studies demonstrated that a majority of patients with CFS have low numbers of NKH1+T3- lymphocytes, a population that represents the great majority of NK cells in normal individuals. CFS patients had normal numbers of NKH1+T3+ lymphocytes, a population that represents a relatively small fraction of NK cells in normal individuals.

When tested for cytotoxicity against a variety of different target cells, patients with CFS consistently demonstrated low levels of killing. After activation of cytolytic activity with recombinant interleukin 2, patients were able to display increased killing against K562 but most patients remained unable to lyse Epstein-Barr virus-infected B cell targets. Additional cytotoxicity experiments were carried out utilizing anti-T3 monoclonal antibody to block killing by NKH1+T3+ cells.

These experiments indicated that the NK cell that appears to be responsible for much of the functional activity remaining in patients with CFS belongs to the NKH1+T3+ subset, which under normal circumstances represents only approximately 20% of the NK cell population.

 

Source: Caligiuri M, Murray C, Buchwald D, Levine H, Cheney P, Peterson D, Komaroff AL, Ritz J. Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. J Immunol. 1987 Nov 15;139(10):3306-13. http://www.ncbi.nlm.nih.gov/pubmed/2824604