Experimental Investigation of Immunoglobulin and Complement Concentrations in Exposure to IVIG, HBIG, Rituximab, Tocilizumab, and Bevacizumab

Abstract

Background: Immunoglobulins (Igs) are produced in plasma cells in response to glycoprotein like immunogens and they are also used as therapeutics in the pharmaceutical industry. It may be important to know the effects of therapeutic Igs on Ig levels during therapy to eliminate any misconceptions about the immunity of patients. Objective: This study aimed to investigate the effects of monoclonal antibody (mAb) derivative drugs and therapeutic antibody (intravenous Ig [IVIG] and hepatitis B immune globulin [HBIG]) treatments on blood IgG, IgA, IgM, IgE, complement component 3 (C3), and complement component 4 (C4) levels. Methods: N Protein Control SL / Low (Siemens, Marburg, Germany, Lot: 084654) was used as the control solution. Aliquots of IVIG, HBIG, rituximab, tocilizumab, and bevacizumab (20 µL) were added to 180 µL of the control solution, and the solutions were vortexed (5 s). The samples were studied using a Dade Behring BN II (Siemens, Marburg, Germany) nephelometer. All measurements were repeated three times by performing the same process in which distilled water (20 µL) was added to the control solution to determine the target value, and the average values were taken. The bias formula was used to calculate the amount by which the results deviated from the target value. Results: IVIG caused the greatest deviation (45.97%) to IgG levels. HBIG, rituximab, tocilizumab, and bevacizumab caused the IgG level to deviate by 0.81%, 9.68%, 27.42%, and 30.65%, respectively. In the IgA test, tocilizumab increased the reading by 8.66%, while the other therapeutics caused reductions in the reading, with the smallest and largest changes caused by HBIG (-0.93%) and bevacizumab (-4.98%). Tocilizumab increased the IgE level by 0.48%, and rituximab and bevacizumab reduced the IgE level by - 0.21% with -8.47%, respectively. Tocilizumab, IVIG, and HBIG caused 1.41%, 2.70%, and 4.32% deviations, respectively, in the C3 levels. Whereas bevacizumab (-1.08%) and rituximab (-5.41%) caused reductions in the C3 levels. Tocilizumab, HBIG, rituximab, IVIG, and bevacizumab caused deviations of 0.87%, -2.31%, -3.76%, -6.36%, -8.38%, respectively, in the C4 levels. Conclusion: Deviations in measured IgG levels after therapeutic Ig and mAb infusions may cause errors in clinical decisions. It is recommended that Ig levels be measured before infusion or when the therapeutic drug has been eliminated from the blood.