Anti-insulin antibody

D-penicillamine has been shown to induce anti-ssDNA and anti-insulin antibodies in C57BL/Ks (H2d) and C3H/He (H2k) but not in BALB/c (H2d) or C57BL/6 (H2b) mice after subcutaneous exposure for 4 weeks [48], Oral exposure to D-penicillamine or quinidine in the drinking water for 7 to 8 months, also caused an increase in levels of auto-antibodies in A.SW/Sn (H2s) mice [49],... 

Immunoassay as an analytical technique was introduced by Rosalind Yalow and Solomon Berson in 1960 with their use of anti-insulin antibodies to measure the concentration of the hormone in plasma. This advance, for which Rosalind Yalow was awarded the Nobel prize, was probably the most important single advance in biological measurement of the following two decades. Examples of the use of immunoassay may now be found in almost all areas of analytical biochemistry. 

Insulin allergy, an immediate type hypersensitivity, is a rare condition in which local or systemic urticaria results from histamine release from tissue mast cells sensitized by anti-insulin IgE antibodies. In severe cases, anaphylaxis results. Because sensitivity is often to noninsulin protein contaminants, the human and analog insulins have markedly reduced the incidence of insulin allergy, especially local reactions. 

A low titer of circulating IgG anti-insulin antibodies that neutralize the action of insulin to a negligible extent develops in most insulin-treated patients. Rarely, the titer of insulin antibodies leads to insulin resistance and may be associated with other systemic autoimmune processes such as lupus erythematosus. 

Several tests use glucagon to diagnose endocrine disorders. In patients with type 1 diabetes mellitus, a classic research test of pancreatic beta-cell secretory reserve uses 1 mg of glucagon administered as an intravenous bolus. Because insulin-treated patients develop circulating anti-insulin antibodies that interfere with radioimmunoassays of insulin, measurements of C-peptide are used to indicate beta-cell secretion. 

A 45-year-old woman who had used insulin for 4 years had a biphasic hypersensitivity reaction to human insulin (or another component of the injection fluid) (135). Within 20 minutes after the injection a swelling developed and in a later phase papular lesions with lichenoid features and post-inflammatory hyperpigmentation emerged. Histologically, there was neutrophilic infiltration with erythrocyte extravasation and eosinophilic amorphous material, surrounded by neutrophilic infiltrate. Saline injection did not elicit an effect. IgE anti-insulin antibodies were not found. There was no Arthus reaction (type IV allergy). 

In patients who have never used other types of insulin, allergic reactions can be seen when human insulin is used and anti-insulin antibodies can be demonstrated... 

Repeated episodes of catheter obstruction by fibrin clots or omental encapsulation can be a problem during continuous peritoneal insulin infusion from implanted pumps (SEDA 20, 397). In the encapsulated tissue, collagen fibrosis, inflammatory reactions with lymphocytes, and amyloid-like deposits reacting to anti-insulin antibodies can occur higher macrophage chemotaxis may also promote these processes. 

A 54-year-old woman and a 62-year-old man with catheter blockages both developed aseptic peritonitis (166). In both cases clots had earlier been removed by laparoscopy, which also showed diffuse thickening around the tip and in the peritoneal fat, with fluid accumulation or inflammation and whitish urticarialike plaques. The tissue was granulomatous, with histiocytes, fibrosis, and pseudo-amyloid material that could not be labeled by anti-insulin antibodies. The peritoneal fluid contained a lot of fibrin, monocytes, lymphocytes, and macrophages, but no bacteria or cancer cells. 

Kim CH, Park JH, Park TS, Baek HS. Autoimmune hypoglycemia in a type 2 diabetic patient with anti-insulin and insulin receptor antibodies. Diabetes Care 2004 27 228-9. 

Usui H, Makino H, Shikata K, Sugimoto T, Wada J, Yamana J, Matsuda M, Yoneda M, Koshima I. A case of congenital generalized lipodystrophy with lipoatrophic diabetes developing anti-insulin antibodies. Diabet Med 2002 19(9) 794-5. 

One of the remarkable autoimmune phenomena that penicillamine can cause is the induction of anti-insulin antibodies, with resultant hypoglycemia (autoimmune hypoglycemia) (924,925). In these patients, there are high concentrations of immunoreactive insulin, despite undetectable free insulin. When penicillamine is withdrawn antibody titers fall sharply. The occurrence of hypoglycemia rather than hyperglycemia is not fully understood (926). 

In two previously well-controlled diabetic patients taking penicillamine who developed hypoglycaemia, no reference was made to anti-insulin antibodies (927). 

Autoimmune hypoglycemia with detectable anti-insulin antibodies, probably caused by pyritinol, has been described in one patient (999). This syndrome has previously been reported in connection with other thiol compounds, (penicillamine, methimazole, and tiopronin). 

Autoimmune hypoglycemia with anti-insulin antibodies, a complication of penicillamine and pyritinol, has also been reported with tiopronin (1124). 

Other problems that may be encountered are related to the immunologic effects of insulin use. Certain forms of insulin may evoke an immune reaction and stimulate antibody production. These anti-insulin antibodies may cause an allergic reaction in some individuals, as well as a resistance to the exogenous insulin molecule. As discussed previously, the incidence of these immunologic reactions seems to be greater when animal (i.e., pork) forms of insulin are used. Consequently, these problems are often resolved by switching the patient to another type of preparation, preferably biosynthetic human insulin. 

A number of disorders are associated with the development of insulin resistance. Although some cases are due to autoimmune responses such as the development of anti-insulin or anti-insulin receptor antibodies, insulin resistance often results from defects at the cellular level in the insulin receptor or in postreceptor function. 

A low titer of circulating IgG anti-insulin antibodies that neutralize the action of insulin to a... 

In the selected example by Lam et al. [101] many peptide libraries were prepared using the mix and split technique and tested in different on-bead screens. Incomplete libraries were tested (the population of most of them was more than a million compounds), and the positive structures were exploited through focused libraries. Some libraries were screened against an anti-insulin monoclonal antibody tagged with alkaline phosphatase, which allowed an enzyme-linked colorimetric detection. Only the beads bound to the murine MAb showed a tourquoise color, while the vast majority remained colorless (details of the technical realization of the assay can be found elsewhere [101, 102]). The chemical structure linked to the positive beads was then easily determined via Edman degradation of the peptide sequences. 

Alternatively, monoclonal antibodies (Mabs) to the relevant receptors can be used as transport vectors. Anti-insulin (Mab83-7 and Mab83-14) and anti-transferrin (0X26) receptor antibodies have been proposed as efficient and selective BBB transport vectors. The antitransferrin receptor antibody binds to a site removed from the transferrin binding site and therefore does not compete with endogenous transferrin for transport across the BBB. Studies using radiolabeled peptides have shown that significant uptake of a... 

Competitive RIA of Free Anti-Insulin Antibodies with PEG Precipitation (Semi-Quantitative Assay)... 

PURPOSE AND RATIONALE Anti-insulin antibodies (ALA) develop in the serum of many patients who are receiving insulin treatment (Berson et al 1956). In addition, insulin auto antibodies (IAA) are detected in insulin dependent diabetes melhtus (IDDM) or Type I Diabetes before insulin therapy (Palmer et al 1986). 

The determination of circulating anti-insulin antibodies is of clinical importance for the following reasons ... 

A blank control (TO) containing no anti-insulin antibodies is used to determine the non-specific binding (NSB). Three titer controls (T1-T3) containing low, medium and high levels of anti-insulin antibodies (guinea pig anti-pore insulin antiserum, e.g. Scant-ibodies Laboratory Inc. T 531 B, Part. 3 AK 025 in buffer solution) are measured in each run. 

A commercially available RIA for determination of free anti-insulin antibodies (CIS bio international) was used for method comparison with insulin tracer binding test for Type I diabetic patients. The CIS test uses a 125I-porcine insulin tracer for insulin antibody determination. Linear regression analysis yielded a correlation coefficient of 0.94 for human insulin antibodies. The absolute binding values were 10-15 % lower in the commercial test than in the in-house test. 

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