Affinity kinetics of leptin-reactive immunoglobulins are associated with plasma leptin and markers of obesity and diabetes

Abstract

Obese subjects display elevated plasma levels of leptin reflecting the phenomenon of leptin resistance. Here, we aimed to determine whether leptin-reactive immunoglobulins (Ig) are present in obese and type 2 diabetes (T2D) patients and whether their plasma levels and affinity kinetics may correlate with obesity and diabetes markers. We show that leptin levels are increased in obese patients with and without T2D. Although mean plasma levels of leptin-reactive IgG were similar between study groups, IgG in obese non-diabetic patients had increased dissociation rate and lower affinity (increased dissociation equilibrium constant value; KD). In controls and diabetic patients, the association rates of leptin IgG correlated negatively with obesity and diabetes markers, respectively. In contrast, KD values correlated positively with plasma leptin levels and obesity traits in our cohort, and with diabetes markers in both the total cohort and in the obese T2D group. Taken together, our data reveal that leptin-reactive IgG are present in healthy subjects, obese, and diabetic patients but display altered affinity kinetics in obesity. Increased IgG binding to leptin in healthy subjects associated with lower body mass index (BMI) suggests an enhancing role of IgG in leptin signaling. Accordingly, a decreased affinity of IgG for leptin, found in obese patients, can be relevant to leptin resistance.

Neurobiology of Aggressive Behavior—Role of Autoantibodies Reactive With Stress-Related Peptide Hormones

“…Although the functional role of peptide hormone-reactive autoabs still needs to be further clarified, it appears that autoabs play a role in the transportation of peptide hormones and cytokines (78–81), and they seem to protect these peptides from degradation by plasma enzymes, thereby preserving biological activity (82).…”

IgG Anti-ghrelin Immune Complexes Are Increased in Rheumatoid Arthritis Patients Under Biologic Therapy and Are Related to Clinical and Metabolic Markers

“…In obese individuals, increased kinetics affinities of IgG antibodies for the orexigenic hormone ghrelin were found and the transfer of these antibodies to mice promoted food intake and body weight gain. Similarly, IgG antibodies directed to the anorexigenic hormone leptin showed decreased affinity in obese humans (28, 48). It is worth mentioning that although there can be changes in the affinity of these ghrelin-reactive autoantibodies its affinity remains at the micromolar range and these can be classified as low-affinity, not being capable of neutralizing the hormone, but instead modulate its transport and/or protect it from degradation by serum enzymes (28).…”

Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders

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