Sulfhydryl‐dependent thermal aggregation of human gamma globulin

Gerber, Donald A.

doi:10.1002/art.1780180112

Cited by 9 publications

(4 citation statements)

References 17 publications

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“…It has been proposed that hypohistidinemia, because of an associated low synovial fluid histidine concentration (26), contributes to the pathogenesis of rheumatoid arthritis by permitting the sulfhydryl-dependent hyaluronate-augmented aggregation of synovial fluid gamma globulin, generating in the joint fluid an inflammatory and antigenic substance (aggregated gamma globulin) (27,28). The observations in the present study are consistent with this hypothesis.…”

Section: Methodssupporting

confidence: 90%

Low free serum histidine concentration in rheumatoid arthritis. A measure of disease activity.

Gerber¹

1975

J. Clin. Invest.

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A B S T R A C T A study of sera from 285 patients with definite or classical rheumatoid arthritis (including 37 patients receiving no anti-inflammatory drugs) and sera from 67 healthy subjects has confirmed 10 published reports of a statistically significant decreased blood histidine concentration in patients with rheumatoid arthritis. Contrastingly, in sera from 231 patients with a variety of acute and chronic illnesses other than rheumatoid arthritis, no statistically significant hypohistidinemia was observed either in the group as a whole or in association with the administration of aspirin, prednisone, indomethacin, phenylbutazone, or dextropropoxyphene.In the patients with rheumatoid arthritis there was a statistically significant correlation between the serum histidine concentration and the following: Westergren sedimentation rate (r = -0.33, P < 10-'), grip strength (r = 0.26, P < 10'), hematocrit (r= 0.23, P < 10-'), duration of morning stiffness (r =-0.14, P = 10-'), walking time (r = -0.13, P = 10"), latex titer of rheumatoid factor (r = -0.11, P = 0.001), and the duration of arthritis (r = -0.06, P = 0.05). There was no statistically significant association between the serum histidine concentration and the duration of rheumatoid arthritis in the 151 patients with disease of 0-10-yr duration (r = 0.02, P = 0.5), the sex of the patient, or the presence of antinuclear antibody (r = 0.007, P = 0.9). The serum histidine concentration was less in rheumatoid patients receiving steroids (P = 0.00001), gold (P = 0.009), and aspirin (P = 0.15) than in rheumatoid patients not receiving these drugs.

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Section: Methodssupporting

confidence: 90%

Low free serum histidine concentration in rheumatoid arthritis. A measure of disease activity.

Gerber¹

1975

J. Clin. Invest.

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“…Although this has not been demonstrated in vivo, Gerber (1974) has shown that IgG did not denature at 63°C if certain molecules were present. Among these were aurothiomalate and penicillamine, and he suggested that they acted by inhibition of the copper catalysed aggregation reaction, possibly by chelating the copper itself.…”

Section: Discussionmentioning

confidence: 89%

“…An effect on the stimulus to rheumatoid factor production has been proposed by Gerber (1975) and Evans (1975) on other grounds and is worth considering in more detail. The reaction between IgG complexes in rheumatoid synovial fluid and IgM rheumatoid factor was demonstrated by Hannestad (1967) and Winchester et al (1970).…”

Section: Discussionmentioning

confidence: 94%

Gold and penicillamine: a proposed mode of action in rheumatoid arthritis, based on synovial fluid analysis.

Pritchard¹,

Nuki²

1978

Annals of the Rheumatic Diseases

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SUMMARY Although in common use, there is still controversy as to the way in which gold and penicillamine act in rheumatoid arthritis (RA).In this study, synovial fluids from 4 groups of patients have been compared: (1) RA patients on gold/penicillamine, (2) RA patients on non-steriodal anti-inflammatory drugs (NSAID) only, (3) osteoarthritis patients, and (4) patients with sero-negative arthropathies. The parameters measured were differential agglutination titre (DAT), total haemolytic complement (CH50), total protein, total white cell count, and immunoglobulins. RA patients on gold/penicillamine have lower synovial DAT levels and higher CH50 levels than RA patients on NSAID only, and total and cryoprecipitable IgM levels very close to those found in the sero-negative joint fluids. The non-specific inflammatory parameters, ie, white cell count and total protein are unchanged after gold/penicillamine therapy.In a second study, the serum DATs of patients in total remission after gold/penicillamine were compared with similar patients on NSAID only. The DAT falls significantly in the former group (P<0 *001), but not in the latter suggesting that fall in DAT is a consequence of therapy rather than remission.The parameters altered by gold/penicillamine in the synovial fluid are those that distinguish RA from non-rheumatoid arthropathies suggesting the drug's primary effect is to render the disease sero-negative. The results support the hypothesis that both drugs have a common mode of action based on their active thiol groups, and that the fall in DAT is due to the reduAtion of the antigenicity of the IgG complexes.

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“…The reaction is probably initiated, at least in part, by the small number [0.2 per molecule of immunoglobulin G (22)] of free sulfhydryl groups normally found in human y-globulin. It has been proposed (20,21) that the gold compounds (23) and chloroquine (24) suppress manifestations of rheumatoid arthritis by suppressing mercaptide anion reactivity, thereby suppressing hyaluronateaugmented sulfhydryl-disulfide interchange-mediated aggregation of synovial fluid y-globulin (21).…”

mentioning

confidence: 99%

Inhibition of denaturation of human gamma globulin by a mixture of l‐histidine, l‐cystine, and copper, and its clinical implication in rheumatoid arthritis

Gerber

1976

Arthritis & Rheumatism

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A mixture of histidine, cystine, and copper mimicked gold thiomalate, N-ethylmaleimide, and pchloromercuribenzoic acid in inhibiting sulfbydryl-disulfide interchange-mediated denaturation of human gamma globulin, bovine serum albumin, and diluted human serum. Measurable inhibitory effects were obtained with a mixture of physiologic concentrations of Lhistidine, Lcystine, and copper. This work suggests a mechanism by which the hypohistidinemia of rheumatoid arthritis could contribute to the pathogenesis of the disease.

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Sulfhydryl‐dependent thermal aggregation of human gamma globulin

Cited by 9 publications

References 17 publications

Low free serum histidine concentration in rheumatoid arthritis. A measure of disease activity.

Low free serum histidine concentration in rheumatoid arthritis. A measure of disease activity.

Gold and penicillamine: a proposed mode of action in rheumatoid arthritis, based on synovial fluid analysis.

Inhibition of denaturation of human gamma globulin by a mixture of l‐histidine, l‐cystine, and copper, and its clinical implication in rheumatoid arthritis

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