Studies on urinary γ‐globulins in patients with rheumatoid arthritis

Gordon, Duncan A.; Eisen, Arthur Z.; Vaughan, John H.

doi:10.1002/art.1780090404

Cited by 18 publications

(13 citation statements)

References 42 publications

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“…Free urinary light chains were found to represent about 40% of the total immunoglobulin components in normal urine. Free light chains occur in both normal plasma and normal urine [51] and apparent.ly originate by de novo synthesis [12,13). In a recent study [26] We found that at neutral pH about 35% to 40% of the free light chains from normal urine occurred as disulfide-linked dimers and about the same amount as non-covalently linked dimers.…”

Section: Discussionmentioning

confidence: 87%

“…It appeared to be of special interest to determine the excretion of free light chains in tubular proteinuria since free urinary light chains have been reported tooriginatefromdenovosynthesis [12,13]andimmunoglobulin producing cells have an intracellular light chain pool which may be important for the regulation of immunoglobulin synthesis [14,15]. The previously observed general difference between urinary proteins from tubular and glomerular proteinuria was also found in the immunoglobulin components.…”

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confidence: 99%

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Urinary Immunoglobulin Components in Normal, Tubular, and Glomerular Proteinuria: Quantities and Characteristics of Free Light Chains, IgG, IgA, and Fcγ Fragment

Peterson

Berggård

1971

Eur J Clin Investigation

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The urinary excretion of free light immunoglobulin chains IgG, IgA, and Fcγ fragment material has been estimated in 12 healthy individuals and 7 subjects with tubular or glomerular proteinuria. Measurements were carried out by immunochemical methods after separation of concentrated urinary immunoglobulin components by gel chromatography. Various components were isolated and their sedimentation constants, Stokes' radii, diffusion coefficients, molecular weights, and frictional ratios were determined.-Twenty-four hour urine volumes from the healthy subjects contained, on average, 3.3 mg of free light chains, 3.0 mg of IgG, approximately 2.0 mg of IgA, and 0.19 mg of Fey fragment Material. Normal urinary IgA included about 90% 11.5 S IgA of molecular weight 370000 and about 10% 7.0 S of molecular Weight 165000.-Patients with tubular proteinuria excreted relatively more of immunoglobulin components of small size than the patients with glomerular proteinuria. In particular, urine from patients with tubular proteinuria contained more free light chains than IgG whereas urine from patients with glomerular proteinuria contained more IgG than free light chains. The excretion of free light chains in the patients with tubular proteinuria was 8 to 33 times the average normal value. The results indicate an excess normal production of light chains assuming that all or most of the free chains originate from de novo synthesis. The relative amounts of urinary 11.5 S and 7.0 S IgA were similar in tubular proteinuria and normal proteinuria, whereas relatively more urinary 7.0 S IgA was found in glomerular proteinuria. This observation and the properties of the two IgA species suggest that the 11.5 S IgA is secretory IgA from the urinary tract and that most or all of the 7.0 S IgA originates from plasma.

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Section: Discussionmentioning

confidence: 87%

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confidence: 99%

Urinary Immunoglobulin Components in Normal, Tubular, and Glomerular Proteinuria: Quantities and Characteristics of Free Light Chains, IgG, IgA, and Fcγ Fragment

Peterson

Berggård

1971

Eur J Clin Investigation

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“…Since the L chain excreted in the urine of normal individuals has been shown to be an anabolic product (38,39), the X-L chain metabolic turnover data can be used to estimate the rate of synthesis of free X-L chains (i.e., X-L chains synthesized but not incorporated into intact In contrast, the metabolism of X-L chains in the five patients with tubular proteinuria studied differed considerably from that of normal individuals (Fig. 6).…”

Section: Resultsmentioning

confidence: 99%

The renal handling of low molecular weight proteins

Waldmann¹,

Strober²,

Mogielnicki³

1972

J. Clin. Invest.

235

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A B S T R A C T The present study was directed toward determining the role of the kidney in the metabolism of various classes of serum proteins and to define the urinary protein excretion patterns and the pathogenesis of disorders of protein metabolism in patients with proteinuria. To this end, the metabolic fates of a small protein, X-L chain (mol wt 44,000), and a protein of intermediate size, IgG (mol wt 160,000), were studied in controls and patients with renal disease. Controls metabolized 0.28%/hr of circulating IgG and 22.3%/hr of circulating X-L chain. All the IgG and 99% of the X-L chain was catabolized with the remaining X-L chain lost intact into the urine. The kidney was shown to be the major site of catabolism for small serum proteins. Three distinct disorders of protein metabolism were noted in patients with renal tubular disease and tubular proteinuria, glomerular disease (the nephrotic syndrome), and disease involving the entire nephrons (uremia), respectively. Patients with renal tubular disease had a 50-fold increase in the daily urinary excretion of 1540,000 molecular weight proteins such as lysozyme and X-L chains. Serum IgG and X-L chain survivals were normal; however, the fraction of the over-all X-L chain metabolism accounted for by proteinuria was increased 40-fold whereas endogenous catabolism was correspondingly decreased. Thus, tubular proteinuria results from a failure of proximal tubular uptake and catabolism of small proteins that are normally filtered through the glomerulus. Patients with the nephrotic syndrome had a slight increase in X-L chain survival whereas IgG survival was decreased and the fraction of IgG lost in the urine was An abstract of this work appeared in J. Clin. Invest. 1970. 49: 99a. (Abstr.)

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“…In recent years, L chains have also been recovered in urine of normal individuals, but their significance is still unclear (27)(28)(29). Isotopic studies suggest that they are products of de nova synthesis and not breakdown products of immunoglobulins (29,30). It is clear from the current and previous studies (17) that the quantity of either L chains or Bence Jones proteins recovered from the urine cannot be taken as an indication of the rate of production of these substances.…”

Section: Discussionmentioning

confidence: 95%

The Role of the Kidney in the Catabolism of Bence Jones Proteins and Immunoglobulin Fragments

Wochner

Strober

Waldmann

1967

The Journal of Experimental Medicine

267

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The role of the kidney in the catabolism of Bence Jones proteins, intact IgG molecules, and isolated L chains, Fab and Fc fragments of IgG, was studied. The proteins were purified, radioiodinated, and their survival times measured in nephrectomized, ureter-severed, and control mice. Active endogenous catabolism was the major factor in overall Bence Jones metabolism since excretion as proteinuria accounted for less than 25% of the total metabolism. The survival times of λ- and κ-type human Bence Jones proteins and the Bence Jones protein produced by mice with MPC-2 plasma cell tumor were exceedingly short in both unoperated and ureter-severed mice, with 50% of the injected protein catabolized in from 0.8–1.6 hr. In contrast, the survival of Bence Jones protein was markedly prolonged in nephrectomized animals, with 50% of the injected dose catabolized in from 9 to 17 hr. This ten-fold decrease in catabolic rate indicates that the kidneys are the major site of breakdown of Bence Jones proteins. Similar studies with other proteins indicated that the kidneys are also the major site for catabolism of isolated L chains but not of intact IgG molecules. The Fc immunoglobulin fragment was not catabolized and the Fab fragment only partially catabolized by the kidney. When ureter-severed animals were allowed to develop advanced uremia before being studied, the survival of Bence Jones protein was greatly prolonged, indicating that the catabolic process is impaired in the presence of uremia. The nature of this renal catabolism remains unknown. These observations suggest that the Bence Jones proteins and L chains observed in the urine of patients may reflect only a small fraction of such molecules synthesized by these patients. Furthermore, they provide an explanation for the prolongation of Bence Jones protein survival and the development of Bence Jones proteinemia observed in subjects with multiple myeloma and impaired renal function.

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Studies on urinary γ‐globulins in patients with rheumatoid arthritis

Cited by 18 publications

References 42 publications

Urinary Immunoglobulin Components in Normal, Tubular, and Glomerular Proteinuria: Quantities and Characteristics of Free Light Chains, IgG, IgA, and Fcγ Fragment

Urinary Immunoglobulin Components in Normal, Tubular, and Glomerular Proteinuria: Quantities and Characteristics of Free Light Chains, IgG, IgA, and Fcγ Fragment

The renal handling of low molecular weight proteins

The Role of the Kidney in the Catabolism of Bence Jones Proteins and Immunoglobulin Fragments

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