Circulating immune complexes in Lyme arthritis. Detection by the 125I-C1q binding, C1q solid phase, and Raji cell assays

J. A. Hardin, L. C. Walker, A. C. Steere, T. C. Trumble, K. S. Tung, R. C. Williams, S. Ruddy, S. E. Malawista

Research output: Contribution to journalArticle

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Abstract

Lyme arthritis is a newly recognized epidemic disease that has been occurring at least since 1972 in southeastern Connecticut and other areas bordering Long Island Sound. It is characterized by recurrent attacks of asymmetric large joint arthritis, by geographic and seasonal clustering, and by the presence of a unique preceding skin lesion, erythema chronicum migrans. We have found immunoglobulin (Ig)G-containing material consistent with immune complexes in the sera of patients with Lyme arthritis. It was detected in 29 of 55 sera (55%) from 31 patients by at least one of three assays: 125I-C1q binding, C1q solid phase, or Raji cell. The presence of reactive material correlated with clinical aspects of disease activity; it was found early in the illness, was most prominent in sera from the sickest patients, was infrequent during remissions, and often fluctuated in parallel with changes in clinical status. The results in the two C1q assays showed a strong positive correlation (P<0.001). They were each elevated in 45% of the sera and were usually concordant (85%). In contrast, the Raji cell assay was less frequently positive and often discordant with the C1q assays. In sucrose density gradients, putative circulating immune complexes sedimented near 19S; they, too, were detected best by the two assays based on C1q binding. An additional 7S component was found in some sera by the 125I-C1q binding assay. Serum complement was often above the range of normal in patients with mild disease and normal in patients with severe disease but did not correlate significantly with levels of circulating immune complexes. IgM and IgG rheumatoid factors were not detectable. These findings support a role for immune complexes in the pathogenesis of Lyme arthritis. Their measurement, by either the 125I-C1q binding assay or by the C1q solid phase assay, often provides a sensitive index of disease activity. Moreover, the complexes are likely sources of disease-related antigens for further study of this new disorder.

Original languageEnglish (US)
Pages (from-to)468-477
Number of pages10
JournalJournal of Clinical Investigation
Volume63
Issue number3
StatePublished - 1979
Externally publishedYes

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Lyme Disease
Antigen-Antibody Complex
Serum
Erythema Chronicum Migrans
Immunoglobulin G
Rheumatoid Factor
Islands
Arthritis
Immunoglobulin M
Cluster Analysis
Sucrose
Reference Values
Joints
Antigens
Skin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hardin, J. A., Walker, L. C., Steere, A. C., Trumble, T. C., Tung, K. S., Williams, R. C., ... Malawista, S. E. (1979). Circulating immune complexes in Lyme arthritis. Detection by the 125I-C1q binding, C1q solid phase, and Raji cell assays. Journal of Clinical Investigation, 63(3), 468-477.

Circulating immune complexes in Lyme arthritis. Detection by the 125I-C1q binding, C1q solid phase, and Raji cell assays. / Hardin, J. A.; Walker, L. C.; Steere, A. C.; Trumble, T. C.; Tung, K. S.; Williams, R. C.; Ruddy, S.; Malawista, S. E.

In: Journal of Clinical Investigation, Vol. 63, No. 3, 1979, p. 468-477.

Research output: Contribution to journalArticle

Hardin, JA, Walker, LC, Steere, AC, Trumble, TC, Tung, KS, Williams, RC, Ruddy, S & Malawista, SE 1979, 'Circulating immune complexes in Lyme arthritis. Detection by the 125I-C1q binding, C1q solid phase, and Raji cell assays', Journal of Clinical Investigation, vol. 63, no. 3, pp. 468-477.
Hardin, J. A. ; Walker, L. C. ; Steere, A. C. ; Trumble, T. C. ; Tung, K. S. ; Williams, R. C. ; Ruddy, S. ; Malawista, S. E. / Circulating immune complexes in Lyme arthritis. Detection by the 125I-C1q binding, C1q solid phase, and Raji cell assays. In: Journal of Clinical Investigation. 1979 ; Vol. 63, No. 3. pp. 468-477.
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abstract = "Lyme arthritis is a newly recognized epidemic disease that has been occurring at least since 1972 in southeastern Connecticut and other areas bordering Long Island Sound. It is characterized by recurrent attacks of asymmetric large joint arthritis, by geographic and seasonal clustering, and by the presence of a unique preceding skin lesion, erythema chronicum migrans. We have found immunoglobulin (Ig)G-containing material consistent with immune complexes in the sera of patients with Lyme arthritis. It was detected in 29 of 55 sera (55{\%}) from 31 patients by at least one of three assays: 125I-C1q binding, C1q solid phase, or Raji cell. The presence of reactive material correlated with clinical aspects of disease activity; it was found early in the illness, was most prominent in sera from the sickest patients, was infrequent during remissions, and often fluctuated in parallel with changes in clinical status. The results in the two C1q assays showed a strong positive correlation (P<0.001). They were each elevated in 45{\%} of the sera and were usually concordant (85{\%}). In contrast, the Raji cell assay was less frequently positive and often discordant with the C1q assays. In sucrose density gradients, putative circulating immune complexes sedimented near 19S; they, too, were detected best by the two assays based on C1q binding. An additional 7S component was found in some sera by the 125I-C1q binding assay. Serum complement was often above the range of normal in patients with mild disease and normal in patients with severe disease but did not correlate significantly with levels of circulating immune complexes. IgM and IgG rheumatoid factors were not detectable. These findings support a role for immune complexes in the pathogenesis of Lyme arthritis. Their measurement, by either the 125I-C1q binding assay or by the C1q solid phase assay, often provides a sensitive index of disease activity. Moreover, the complexes are likely sources of disease-related antigens for further study of this new disorder.",
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AU - Hardin, J. A.

AU - Walker, L. C.

AU - Steere, A. C.

AU - Trumble, T. C.

AU - Tung, K. S.

AU - Williams, R. C.

AU - Ruddy, S.

AU - Malawista, S. E.

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N2 - Lyme arthritis is a newly recognized epidemic disease that has been occurring at least since 1972 in southeastern Connecticut and other areas bordering Long Island Sound. It is characterized by recurrent attacks of asymmetric large joint arthritis, by geographic and seasonal clustering, and by the presence of a unique preceding skin lesion, erythema chronicum migrans. We have found immunoglobulin (Ig)G-containing material consistent with immune complexes in the sera of patients with Lyme arthritis. It was detected in 29 of 55 sera (55%) from 31 patients by at least one of three assays: 125I-C1q binding, C1q solid phase, or Raji cell. The presence of reactive material correlated with clinical aspects of disease activity; it was found early in the illness, was most prominent in sera from the sickest patients, was infrequent during remissions, and often fluctuated in parallel with changes in clinical status. The results in the two C1q assays showed a strong positive correlation (P<0.001). They were each elevated in 45% of the sera and were usually concordant (85%). In contrast, the Raji cell assay was less frequently positive and often discordant with the C1q assays. In sucrose density gradients, putative circulating immune complexes sedimented near 19S; they, too, were detected best by the two assays based on C1q binding. An additional 7S component was found in some sera by the 125I-C1q binding assay. Serum complement was often above the range of normal in patients with mild disease and normal in patients with severe disease but did not correlate significantly with levels of circulating immune complexes. IgM and IgG rheumatoid factors were not detectable. These findings support a role for immune complexes in the pathogenesis of Lyme arthritis. Their measurement, by either the 125I-C1q binding assay or by the C1q solid phase assay, often provides a sensitive index of disease activity. Moreover, the complexes are likely sources of disease-related antigens for further study of this new disorder.

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