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Dysfunction of natural killer activity in a family with Chronic Fatigue Syndrome (CFS)

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A family was identified with 5 of 6 siblings and 3 other immediate

family members who had developed chronic fatigue syndrome

(CFS) as adults. All 8 met criteria for the CFS case

definition as recommended by the Centers for Disease Control

and Prevention.

Sixty-eight blood samples were obtained over a

period of 2 years from 20 family members (8 affected, 12

unaffected) and 8 normal controls. All blood samples were

tested for NK activity in 4-h 51Cr-release assays and for the

number of circulating CD3-CD56(+) and CD3-CD16(+) by flow

cytometry. NK activity of the affected immediate family

members (cases, n = 8) was significantly lower (P = 0.006,

two-sided) than that of the concurrently tested normal

controls. The results for unaffected family members were

intermediate between these two groups, and the pairwise

comparison of unaffected family members to either cases or

controls showed no statistically significant difference (P =

0.29, two-sided). No differences were seen between the groups

in the absolute number of CD3-CD56(+) or CD3-CD16(+)

lymphocytes in the peripheral blood.

Familial CFS was

associated with persistently low NK activity, which was

documented in 6/8 cases and in 4/12 unaffected family members.

In the family with 5 of 6 siblings who had documented CFS, 2

of their offspring had pediatric malignancies. Low NK activity

in this family may be a result of a genetically determined

immunologic abnormality predisposing to CFS and cancer.

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