Low NK cell cytotoxic activity in autism: glutathione, IL-2 and IL-15

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*1: J Neuroimmunol. 2008* Dec 15;205(1-2):148-54. Epub 2008 Oct

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Low natural killer cell cytotoxic activity in autism: The role

of glutathione, IL-2 and IL-15.

Vojdani A, Mumper E, Granpeesheh D, Mielke L, Traver D, Bock K,

Hirani K, Neubrander J, Woeller KN, O'Hara N, Usman A, Schneider C,

Hebroni F, Berookhim J, McCandless J.

Immunosciences Lab., Inc., 10350 Santa Blvd., Ste. 205, Los

Angeles, CA 90025, United States.

Although many articles have reported immune abnormalities in autism,

NK cell activity has only been examined in one study of 31 patients,

of whom 12 were found to have reduced NK activity. The mechanism

behind this low NK cell activity was not explored. For this reason,

we explored the measurement of NK cell activity in 1027 blood

samples from autistic children obtained from ten clinics and

compared the results to 113 healthy controls. This counting of NK

cells and the measurement of their lytic activity enabled us to

express the NK cell activity/100 cells. At the cutoff of 15-50 LU we

found that NK cell activity was low in 41-81% of the patients from

the different clinics. This NK cell activity below 15 LU was found

in only 8% of healthy subjects (p<0.001). Low NK cell activity in

both groups did not correlate with percentage and absolute number of

CD16(+)/CD56(+) cells. When the NK cytotoxic activity was expressed

based on activity/100 CD16(+)/CD56(+) cells, several patients who

had displayed NK cell activity below 15 LU exhibited normal NK cell

activity. Overall, after this correction factor, 45% of the children

with autism still exhibited low NK cell activity, correlating with

the intracellular level of glutathione. Finally, we cultured

lymphocytes of patients with low or high NK cell activity/cell with

or without glutathione, IL-2 and IL-15. The induction of NK cell

activity by IL-2, IL-15 and glutathione was more pronounced in a

subgroup with very low NK cell activity. We conclude that that 45%

of a subgroup of children with autism suffers from low NK cell

activity, and that low intracellular levels of glutathione, IL-2 and

IL-15 may be responsible.

PMID: 18929414