The "L.E.-CELL" Phenomenon in Active Chronic Viral Hepatitis

Joske, R. A.; King, William E.

doi:10.1016/s0140-6736(55)93331-6

Cited by 159 publications

(27 citation statements)

References 18 publications

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“…In rheumatoid arthritis, LE cell positivity has been observed about as frequently as histone H1 antibody positivity (35). The occurrence of LE cells in nonrheumatologic diseases such as hepatitis (37) and lymphoma (38) is especially surprising and may be due to the presence of histone H1 antibodies. In addition, in procainamide-and hydralazine-induced lupus, autoantibodies against histone H1 (39,40) and positive LE cell phenomenon (41) are found with similar frequencies (50%).…”

Section: Discussionmentioning

confidence: 99%

Nuclear antigen histone H1 is primarily involved in lupus erythematosus cell formation

Schett

Steiner

Smolen

1998

Arthritis & Rheumatism

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Objective. To elucidate the nature of the antigen reactive with the "lupus erythematosus (LE) cell factor," the autoantibody involved in the LE cell phenomenon.Methods. Serum samples from systemic lupus erythematosus (SLE) patients who were positive for the LE cell phenomenon (LEc+) and SLE patients who were negative for the LE cell phenomenon (LEc-) were used to characterize the nuclear antigen bound by the LE cell factor, by immunoblotting and immunoprecipitation techniques.Results. All LEc+ sera, but none of the LEcsera, uniformly reacted with a double band of M W -30 kd in nuclear extracts. Depletion of nuclear protein extracts of antigens bound by pooled LEc-serum allowed precipitation of a low molecular weight protein by pooled LEc+ serum. This protein was able to block LE cell formation by LEc+ serum. Based on its reactivity with antihistone antibody and an electrophoretic mobility identical with that of precipitated and purified histone H1, this protein was identified as histone H1. Moreover, all LEc+ sera, but none of the LEc-sera, reacted with purified histone H1 by immunoblotting, whereas other histones were reactive with both types of sera. In addition, purified histone H1, but none of the other histones, strongly inhibited the induction of LE cells by LEc+ serum.Conclusion. Histone H1 represents the major antigenic component recognized by the LE cell factor. Thus, the LE cell phenomenon appears to be due primarily to anti-histone H1 reactivity.The lupus erythematosus (LE) cell phenomenon was recognized 50 years ago by Hargraves et a1 (1) constituted one of the first laboratory abnormalities ever found to be associated with systemic lupus erythematosus (SLE). It requires the presence of cell nuclei released from traumatized cells that usually have lost the normal chromatin pattern (2), antibodies originally termed LE cell factor (3), and complement (4). The ensuing engulfment of the opsonized nuclear material by polymorphonuclear cells leads to the classic appearance of the LE cell.After its original description, the elucidation of the mechanisms responsible for and related to LE cell formation became the center of interest for a generation of immunologists and rheumatologists. Kunkel, Holman, and Deicher observed that the LE cell factor was reactive with deoxyribonucleoproteins of the cell nucleus (5-7) and that it could be associated with pathologic events in SLE (8,9). Thus, the LE cell phenomenon was the first antinuclear antibody reactivity ever described and gave rise to a still-growing list of known autoantibodies to nuclear constituents. Meanwhile, several dozen nuclear antigens have been characterized and shown to react with autoantibodies from patients with SLE and various other rheumatic diseases (10-13).In spite of these advances, the autoantigen reactive with the LE cell factor has not been characterized, and the reactivities of the LE cell factor that are best known to date are the originally described and later confirmed ones with nucleosomes (5-7,14,15) which contain DNA and histones...

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Section: Discussionmentioning

confidence: 99%

Nuclear antigen histone H1 is primarily involved in lupus erythematosus cell formation

Schett

Steiner

Smolen

1998

Arthritis & Rheumatism

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“…This was a 36-year-old woman, described further in 1955 in a case study by Joske and King [16] as active chronic viral hepatitis with positivity for the lupus erythematosus (L.E.) cell test.…”

Section: Early Days: 1940s-1950smentioning

confidence: 94%

Historical reflections on autoimmune hepatitis

Mackay

2008

WJG

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Autoimmune hepatitis (AIH), initially known as chronic active or active chronic hepatitis (and by various other names), first came under clinical notice in the late 1940s. However, quite likely, chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver. An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E. cell test positivity and emphasized accompanying multisystem features and immunological aberrations. Yo u n g w o m e n f e a t u r e d p r o m i n e n t l y i n e a r l y descriptions of CAH. AIH was first applied in 1965 as a descriptive term. Disease-characteristic autoantibodies were defined from the early 1960s, notably antinuclear antibody (ANA), smooth muscle antibody (SMA) and liver-kidney microsomal (LKM) antibody. These are still widely used diagnostically but their relationship to pathogenesis is still not evident. A liver and disease specific autoantigen has long been searched for but unsuccessfully. Prolonged immunosuppressive therapy with prednisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today. AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8, DR3 haplotype, and also with DR4. Looking forwards, AIH is one of the several enigmatic autoimmune diseases that, despite being (relatively) organ specific, are marked by autoimmune reactivities with non-organ-specific autoantigens. New paradigms are needed to explain the occurrence, expressions and pathogenesis of such diseases.

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“…Derartige A ntikörper, die sich während und vor allem nach entzündlichen Lebererkrankungen nachweisen lassen, werden von Vorländer, Scheiffarth u. a. weniger als Ursache, vielm ehr als Folge des Krankheitsprozesses angesehen [103,118]. Auch Joske und King u. a. haben diese Zusam m enhänge für den Fall der LEpositiven H epatitis ähnlich gedeutet [59,72,73]. Es erhebt sich also die Frage nach dem Ausmaß und der klinischen B edeutung von Im m unreaktionen im Verlaufe von Lebererkrankungen, die prim är keine autoim m une Pathogenese haben -insbesondere für die weitere U nter haltung des Krankheitsprozesses.…”

Section: Kriterien Fü R Die Diagnose Der Lupoiden Hepatitisunclassified

Das Syndrom der «lupoiden Hepatitis»

Harders¹,

Dölle²

1963

Digestion

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The "L.E.-CELL" Phenomenon in Active Chronic Viral Hepatitis

Cited by 159 publications

References 18 publications

Nuclear antigen histone H1 is primarily involved in lupus erythematosus cell formation

Nuclear antigen histone H1 is primarily involved in lupus erythematosus cell formation

Historical reflections on autoimmune hepatitis

Das Syndrom der «lupoiden Hepatitis»

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