Transfer of human serum IgG to ... mice ... role for autoantibodies in the loss of secretory function.. in Sjögren’s syndrome 1998, Robinson et al

Hutan · Jun 3, 2024

Transfer of human serum IgG to nonobese diabetic Igμnull mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjögren’s syndrome - link

Christopher P. Robinson,* Jason Brayer,* Shigeo Yamachika,* Thomas R. Esch,† Ammon B. Peck,‡§Carol A. Stewart,§¶ Elisabeth Peen,‖ Roland Jonsson,** and Michael G. Humphreys-Beher*§‡‡

The NOD (nonobese diabetic) mouse has been studied as an animal model for autoimmune insulin-dependent diabetes and Sjögren’s syndrome. NOD.Igμnull mice, which lack functional B lymphocytes, develop progressive histopathologic lesions of the submandibular and lachrymal glands similar to NOD mice, but in the absence of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in salivary and lachrymal tissues, NOD.Igμnull mice fail to lose secretory function as determined by stimulation of the muscarinic/cholinergic receptor by the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating exocrine dryness.

Infusion of purified serum IgG or F(ab′)2 fragments from parental NOD mice or human primary Sjögren’s syndrome patients, but not serum IgG from healthy controls, alters stimulated saliva production, an observation consistent with antibody binding to neural receptors.

Furthermore, human patient IgG fractions competitively inhibited the binding of the muscarinic receptor agonist, [3H]quinuclidinyl benzilate, to salivary gland membranes. This autoantibody activity is lost after preadsorption with intact salivary cells. These findings indicate that autoantibodies play an important part in the functional impairment of secretory processes seen in connection with the autoimmune exocrinopathy of Sjögren’s syndrome.

Hutan · Jun 3, 2024

I thought people might be interested in this 1998 paper, in the light of the recent studies claiming to transfer Long Covid symptoms to mice via IgG from Long Covid blood. I wonder what came of this research.

Treatment with IgG from four different Sjögren’s syndrome sera (#77, #36, #93, and #45) resulted in an average 54% decrease in saliva volumes generated, relative to the control, after 24 hr (Fig. (Fig.33B; P < 0.001).
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These researchers did not pool human sera samples.

Transfer of Secretory Gland Dysfunction with Serum IgG Fractions.
Both primary Sjögren’s syndrome patients and NOD mice produce autoantibodies that interact with the autonomic nervous system receptors responsible for initiating the secretory response (17–19). To determine the potential for IgG antibodies to transfer exocrine tissue dysfunction to young NOD.Igμnull mice, a series of transfer experiments was performed in which IgG from healthy control mice and healthy humans, prediabetic NOD mice, as well as human Sjögren’s syndrome patients were infused into NOD.Igμnull mice. As indicated in Fig. Fig.33A and B, mice given a single infusion of IgG from nondisease mice or healthy human sera retained near-normal secretory function at 24 hr (P > 0.05; n = 4) after secretory stimulation with a secretagogue mixture of β-adrenergic and muscarinic/cholinergic receptor agonists (8). Mice treated with IgG isolated from older, parental NOD/Lt mice secreted only 30% of the saliva volume normally generated. Treatment with IgG from four different Sjögren’s syndrome sera (#77, #36, #93, and #45) resulted in an average 54% decrease in saliva volumes generated, relative to the control, after 24 hr (Fig. (Fig.33B; P < 0.001). A 37% decline was noted when purified F(ab′)2 fragments from autoimmune patients were given to mice at a concentration of 10 μg/animal. Injection of the Sjögren’s syndrome sera IgG into an unrelated mouse strain, C57BL/6-scid, again resulted in a decrease in secretory response after challenge with secretory agonists (Fig. (Fig.33B).
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Transfer of human serum IgG to ... mice ... role for autoantibodies in the loss of secretory function.. in Sjögren’s syndrome 1998, Robinson et al

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Transfer of human serum IgG to ... mice ... role for autoantibodies in the loss of secretory function.. in Sjögren’s syndrome 1998, Robinson et al

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