Comparative study of immune status to infectious agents in elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance

Abstract

Whereas patients with multiple myeloma (MM) have a well-documented susceptibility to infections, this has been less studied in other B-cell disorders, such as Waldenstrom's macroglobulinemia (WM) and monoclonal gammopathy of undetermined significance (MGUS). We investigated the humoral immunity to 24 different pathogens in elderly patients with MM (n = 25), WM (n = 16), and MGUS (n = 18) and in age-matched controls (n = 20). Antibody titers against pneumococci, staphylococcal alpha-toxin, tetanus and diphtheria toxoids, and varicella, mumps, and rubella viruses were most depressed in MM patients, next to lowest in WM and MGUS patients, and highest in the controls. In contrast, levels of antibodies specific for staphylococcal teichoic acid, Moraxella catarrhalis, candida, aspergillus, and measles virus were similarly decreased in MM and MGUS patients. Comparable titers in all study groups were seen against Haemophilus influenzae type b (Hib), borrelia, toxoplasma, and members of the herpesvirus family. Finally, a uniform lack of antibodies was noted against Streptococcus pyogenes, salmonella, yersinia, brucella, francisella, and herpes simplex virus type 2. To conclude, although MM patients displayed the most depressed humoral immunity, significantly decreased antibody levels were also evident in patients with WM and MGUS, particularly against Staphylococcus aureus, pneumococci, and varicella. Conversely, immunity was retained for Hib and certain herpesviruses in all study groups.

Fig. 1.

Stepwise antibody titer pattern. (A) Anti-staphylococcal IgG antibody titers to alpha-toxin. Each triangle represents one individual. Open triangles represent treatment-naïve MM patients (n = 3) and WM patients (n = 8). Horizontal bars denote the median value for each study group. The dotted lines indicate age-stratified population medians; the upper line for those age >75 years, the lower for the 60-to-75-year bracket. (B) Anti-pneumococcal IgG antibody titers to pneumococcal polysaccharide (PPS). The dotted line indicates the control group median antibody level. (C) Anti-tetanus and anti-diphtheria toxoid IgG. The bars and error bars indicate group median titers and interquartile ranges. Numbers enclosed in the bars represent percentage with protective immunity, in the case of diphtheria short-term immunity. **, P < 0.01, versus MGUS; ***, P < 0.001, versus control group. (D) Anti-varicella-zoster virus (VZV) IgG. The dotted line indicates the cutoff level for protective immunity (400). ***, P < 0.001.

Fig. 2.

Antibody titers most depressed in MM and MGUS patients. Each triangle represents one individual. Open triangles represent treatment-naïve MM patients (n = 3) and WM patients (n = 8). Horizontal bars denote the median value for each study group. (A) Anti-staphylococcal IgG antibody titers to teichoic acid. The dotted line indicates a population median for those age ≥60 years. (B) Anti-moraxella IgG (OD value) measured in serum samples diluted 1:80. The dotted line indicates the control group median OD level. (C) Anti-candida IgG. Titers between the dotted lines (40 to 100) are considered borderline, titers <40 are considered negative, and titers >100 are considered positive with respect to ongoing infection. (D) Anti-aspergillus IgG. Titers between the dotted lines (50 to 70) are considered borderline, titers <50 are considered negative, and titers >70 are considered positive. **, P < 0.01; ***, P < 0.001.

Fig. 3.

Comparable antibody titers among all study groups. Each triangle represents one individual. Open triangles represent treatment-naïve MM patients (n = 3) and WM patients (n = 8). Horizontal bars denote the median value for each study group. (A) Anti-Haemophilus (Hib) IgG. The dotted line (0.15) represents a minimum protective antibody level. (B) Anti-borrelia IgG; (C) anti-herpes simplex virus (HSV) IgG; (D) anti-toxoplasma IgG. In panels B to D, the dotted lines indicate the levels of seropositivity; 15 AU/ml (B), 400 AU/ml (C), 100 AU/ml (D).