Altered immunoglobulin metabolism in systemic lupus erythematosus and rheumatoid arthritis

Levy, Joshua; Barnett, Eugene V.; MacDonald, Norman S.; Klinenberg, James R.

doi:10.1172/jci106283

Cited by 57 publications

(27 citation statements)

References 34 publications

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“…An important factor influencing serum Ig levels is the balance between synthetic and catabolic rate of different Ig isotypes. IgG catabolism is greater in patients with SLE than in patients with RA, whereas IgM catabolism is greater in RA compared to patients with SLE 35.…”

Section: Discussionmentioning

confidence: 81%

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Reddy

Martinez

Isenberg

et al. 2017

Arthritis Care & Research

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ObjectiveB cell–depletion therapy based on rituximab is a therapeutic option for refractory disease in patients with systemic lupus erythematosus (SLE). The aim of this observational study was to document long‐term effects on B cell function by following serum immunoglobulin levels in patients with SLE treated with rituximab in routine clinical practice.MethodsWe included 57 consecutive patients with SLE treated with rituximab and concomitant/sequential immunosuppressants and measured serum total IgG, IgM, and IgA and IgG anti‐dsDNA antibodies, over a median of 48 months most recent followup. Flow cytometry was used prospectively to assess B cell phenotypes in 17 of 57 patients.ResultsTwelve patients (21%) had persistent IgM hypogammaglobulinemia (<0.4 gm/liter), and 4 of 57 (5%) had low IgG (<7 gm/liter) at the most recent followup (range 12–144 months). This was not associated with serious adverse events or high anti–double‐stranded DNA (anti‐dsDNA) antibodies (>1,000 IU/ml; normal <50 IU/ml). Factors predictive of low serum IgM included baseline serum IgM ≤0.8 gm/liter (receiver operator curve analysis) and subsequent therapy with mycophenolate mofetil (MMF; odds ratio 6.8, compared with other immunosuppressants). In patients maintaining normal IgM levels (9 of 17), the frequency of circulating IgD+CD27+ B cells was significantly higher (P = 0.05). At 12 months after rituximab, 7 of 30 SLE patients with baseline anti‐dsDNA ≤1,000 IU/ml had lost seropositivity.ConclusionLower baseline serum IgM levels and sequential therapy with MMF were predictive of IgM hypogammaglobulinemia after rituximab in SLE, but this was not associated with higher levels of anti‐dsDNA antibodies or an increased risk of infections. This provides useful directions for clinicians regarding rituximab and sequential immunosuppressive treatment for patients with SLE.

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Section: Discussionmentioning

confidence: 81%

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Reddy

Martinez

Isenberg

et al. 2017

Arthritis Care & Research

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“…Raised levels of IgG in the setting of SLE are clearly attributable to increased production (5). Indeed, catabolism of IgG is reported to be enhanced in SLE (12), leading to calculations that increases in the rate of production as great as 3-4-fold might be occurring (13). Relatives of patients with SLE also produce high levels of IgG in response to pokeweed mitogen (9).…”

Section: Discussionmentioning

confidence: 99%

Natural killer T cells in families of patients with systemic lupus erythematosus: Their possible role in regulation of IGG production

Green¹,

Kennell²,

Larché³

et al. 2007

Arthritis & Rheumatism

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Objective. To determine whether there is a link between the frequency of natural killer T (NKT) cells and high levels of IgG in patients with systemic lupus erythematosus (SLE) and their relatives.Methods. Blood samples were obtained from patients with SLE, their first-degree relatives, patients with rheumatoid arthritis (RA), and healthy control subjects. The frequency of NKT cells (defined as CD56؉ T cells) was expressed as a percentage of total blood lymphocytes. Plasma levels of total IgG and IgM, and IgG antibodies to double-stranded DNA (dsDNA) were determined.Results. The frequency of NKT cells was lower in patients with SLE than in control subjects. No such decrease was observed in the relatives of patients with SLE or in patients with RA. High levels of IgG were observed in both patients with SLE and their relatives, while low levels of IgM were observed in these same groups. In relatives of patients with SLE, an inverse correlation between the frequency of NKT cells and IgG levels was observed. Moreover, raised levels of IgG in patients with SLE and their relatives and high levels of IgG anti-dsDNA in patients were associated with low frequencies of NKT cells. Conclusion.These results suggest that NKT cells have an important role in the regulation of IgG production, although NKT cells with invariant T cell receptors may not necessarily be involved. NKT cells in the setting of SLE could lack the cytokine stimulus from NK or other cells that is needed to exert control on IgG production. Enhancement of NKT cell activity may provide a novel basis for therapy in SLE.

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“…Each HRA and none of the control preparations was positive (Table IV). In both groups, the daily FCR (U/P) was consistent through study days [1][2][3][4][5][6][7][8][9][10] (Table IV). These results are discussed below (see Discussion).…”

mentioning

confidence: 89%

“…The increased FCRs found by previous workers did not correlate with laboratory indices of disease, such as rheumatoid factor (RF) titers or erythrocyte sedimentation rates (ESR) (5,6,10,11). One of these groups (11) Tables I and II list the characteristics of the subjects studied.…”

mentioning

confidence: 94%

Metabolism of Autologous and Homologous IgG in Rheumatoid Arthritis

Catalano¹,

Krick²,

Heer³

et al. 1977

J. Clin. Invest.

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A B S T R A C T The metabolism of radioiodinated IgG was studied in 20 patients with rheumatoid arthritis and 11 normal controls using autologous IgG and homologous IgG pooled from normal donors. Fractional catabolic rates in the controls were 4.44% of the autologous-and 4.29% of the homologouslabeled protein per day. The corresponding rates in the rheumatoid patients were 9.67% of the autologousand 8.64% of the homologous-labeled protein per day. Extravascular catabolism occurred only in the rheumatoid group and accounted essentially for the entire increased catabolism ofIgG observed in these patients. 10 patients were especially hypercatabolic, with fractional catabolic rates for autologous IgG greater than 10%. Moreover, they catabolized their autologous IgG significantly faster than the homologous IgG (12.6 vs. 9.9%). The increment of catabolism of autologous over homologous IgG also occurred in the extravascular compartment. These highly hypercatabolic patients had a significantly increased number of manifestations of extra-articular disease.The hypercatabolism of IgG could not be correlated with age, weight, sex, duration of disease, joint erosions, corticosteroid therapy, erythrocyte sedimentation rate, rheumatoid factor titer, serum IgG concentration, or circulating immune complexes as measured by the Raji cell radioimmunoassay.Conceivable sites of extravascular catabolism and possible causes of faster catabolism of autologous (rheumatoid) than of homologous (normal) IgG are discussed.

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Altered immunoglobulin metabolism in systemic lupus erythematosus and rheumatoid arthritis

Cited by 57 publications

References 34 publications

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Natural killer T cells in families of patients with systemic lupus erythematosus: Their possible role in regulation of IGG production

Metabolism of Autologous and Homologous IgG in Rheumatoid Arthritis

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