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High frequency of autoantibodies to insoluble cellular antigens in patients with Chronic Fatigue Syndrome (CFS)

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By von Mikecz A, Konstantinov K, Buchwald DS, Gerace L, Tan EM • • February 10, 1997

OBJECTIVE: To elucidate the humoral immune response in
patients with chronic fatigue syndrome (CFS), by
identification and characterization of autoantibodies.

METHODS: Initial immunofluorescence histochemistry studies of
sera using human HEp-2 cell substrate were followed by
antibody class subtyping and colocalization studies with
reference antibodies. Association of CFS autoantigens with
insoluble cellular components was determined by in situ
extraction of soluble components and subsequent
immunofluorescence histochemistry studies on the extracted
cell substrate.

RESULTS: Of 60 CFS patients, 41 (68%) were
positive for antinuclear antibodies. Localization of nuclear
staining was found at the nuclear envelope (52%), in
reticulated speckles (25%), in nucleoli (13%), and in dense
fine speckles (5%). Twenty-eight CFS sera (47%) also had
antibodies to cytoplasmic antigens. The major cytoplasmic
staining pattern was of the intermediate filament type (35%).
The observed nuclear envelope pattern of staining
co-localized with lamina-associated polypeptide 2 (an
integral nuclear membrane protein), the reticulated speckle
pattern co-localized with non-small nuclear RNP splicing
factor SC-35, and the intermediate filament pattern
co-localized with vimentin. The intermediate filament antigen
was shown to be vimentin in immunoblotting experiments using
recombinant human vimentin, and one of the nuclear envelope
antigens was shown previously to be lamin B1. Fifty of the 60
CFS patients (83%) had antibodies to one or another of these
antigens, all of which are relatively insoluble cellular
antigens, whereas a control group of patients without chronic
fatigue had a significantly lower frequency of such antibodies

CONCLUSION: The high frequency of autoantibodies to
insoluble cellular antigens in CFS represents a unique feature
which might help to distinguish CFS from other rheumatic
autoimmune diseases.

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