Antibodies patient characteristics

Gender, age, and ethnic background have all been reported to influence the incidence of antibody response to specific therapeutic proteins. However, the only patient characteristic that consistently has been identified for a number of different products is the disease that the patients suffer from. Cancer patients are less likely to produce antibodies to therapeutic protein than other patients. The most widely accepted explanation for this difference is the immune-compromised state of cancer patients, both by the disease as by anticancer treatment. Also the median survival of patients on treatment by therapeutic proteins may be too short to develop an antibody response. In any case, cancer reduces the probability of an antibody response to a protein considerably. 

Patient characteristics can also be an important factor in determining whether antibodies will be produced. For example, cancer patients, whose immune response may be impaired due to their disease and treatment with myelosuppressive chemotherapy, would presumably have a lower incidence of antibodies, as might any patient whose disease or treatment lowers immune response. It should be noted, however, that even cancer patients are capable of expressing antibodies to foreign proteins (35). 

Patient characteristics, such as genetic background and the disease status, are known to influence rate and type of immune reactions [11]. Hemophilia patients with severe genetic defects are more prone to antibody formation than patients with minor genetic defects [30, 31]. Eprex (Ortho Biotech, Tilburg, The Netherlands) associated pure red cell aplasia (PRCA) was only observed in patients with renal failure and not in cancer patients [32]. 

Patients with dialysis dementia respond positively to an antibody against the hyperphosphorylated microtubule-associated protein, tau, that accumulates in AD tangles (Guy et al. 1991). The neurofilament protein tubulin contains an acidic tau binding site to which Al might bind to cause tau accumulation. However, not only do dialysis dementia patients characteristically show no tangle formation, but the tangles seen in animals treated with Al are predominantly made up of neurofilament subunits such as tubulin, rather than microtubule-associated protein. A potential role for Al in G-protein-regulated neurofilament polymerization is discussed in Sect. G. 

Among overlap syndromes, ILD seems to be particularly frequent in patients with sclero(dermato)myositis. Sclero(dermato)myositis differs from MCTD by the absence of features of SLE (327). The anti-PM/Scl antibody is characteristic, although also found in PM, DM, or SSc without feamres of overlap syndromes (328). The reported prevalence of ILD in patients with this antibody is variable, reaching 85% in one series (Fig. 16) (329). Despite the high frequency of ILD, patients with the anti-PM/Scl antibody have a favorable outcome (329). 

Mastocytosis is recognized in most patients because of the presence of characteristic cutaneous lesions [10]. A positive Darier s sign and/or histological examination of the skin using metachromatic stains, or by immunohistochemistry using antibodies to mast cell tryptase, helps confirm the diagnosis of cutaneous disease. 

Glial cytoplasmic inclusions are strongly immunoreac-tive for a-synuclein and filaments isolated from the brains of patients with multiple system atrophy are labeled by a-synuclein antibodies [10]. As in dementia with Lewy bodies, assembled a-synuclein is nitrated and phosphory-lated at S129, and the number of a-synuclein-positive structures exceeds that stained by anti-ubiquitin antibodies, confirming that the accumulation of a-synuclein precedes ubiquitination. Filament morphologies and their staining characteristics were found to be similar to those of filaments extracted from the brains of patients with Parkinson s disease and dementia with Lewy bodies. 

The IgA banding patterns are seen in the pH 4.5-6.0 region in polyacrylamide gel after protein separation by isoelectric focusing. It was observed in the CSF of multiple sclerosis patients that the intrathecally synthesized viral antibodies of IgG and IgM classes possess oligoclonal characteristics, whereas IgA antibodies appeared to be polyclonal (M3). 

The antibody-dependent lysis of tumor cells by PMNs exhibited some of the characteristics of damage mediated by products of the burst in the presence of tumor cells there was increased consumption of O2, increased formation of O and activation of the hexose monosphosphate shunt However, although a reduction in the concentration of O2 in the medium inhibited lysis neither catalase nor superoxide dismutase inhibited. The lack of effect on these enzymes was attributed to their inability to interpose themselves between the plasma membranes of the PMN and its target. Similar conclusions were reached by Clark, and Klebanoff whose data incriminated the products of the burst by the reduced killing of tumor cells by PMNs from patients with chronic granulomatous disease. Myeloperoxidase, however, appeared not to he required since neither azide or cyanide inhibited and killing by PMNs from patients with inherited deficiency of myeloperoxidase was normal. 

Nakajima-Adachi, H., Hachimura, S., Ise, W., Honma, K., Nishiwaki, S., Hirota, M. et al. 1998. Determinant analysis of IgE and IgG4 antibodies and T cells specific for bovine alpha(s)l-casein from the same patients allergic to cow s milk existence of alpha(s)l-casein-specific B cells and T cells characteristic in cow s-milk allergy. J Allergy Clin Immunol 101(5) 660—671. 

In the face of so much evidence that the immune response in gonococcal infection is irrelevant, nonprotective, or even deleterious are observations that indicate that the host response does participate in the resolution of infection. In vitro, antibody- and complement-mediated lysis is an effective bactericidal mechanism (R4, S9). DGI, unlike local infections, does appear to protect against dissemination on subsequent exposure (R14), and patients with deficiencies of terminal complement components are particularly prone to disseminated infection (P8). By and large, characteristics of the bacteria, rather than host factors, appear to be more important in allowing gonococci to elude immune destruction and cause local, locally invasive, or dissemi-... 

The isolation of disease-related antibodies specific for either melanoma [ 180], the autoimmune thyroid peroxidase antigen [174], or neutrophil antigen characteristic of ulcerative colitis [17] from nonnaive patient repertoire phage libraries has been reviewed above in the Panning on cells section. The isolation of anti-viral antibodies with diagnostic or therapeutic potential from antibody repertoire libraries has been described in earlier papers e.g. against HIV [197], hepatitis B virus [198] and human respiratory syncytial virus [199],... 

Polyneuropathy with both sensory and motor involvement is much more common among cancer patients than pure SN [83, 110, 111]. SCLC is the most common associated tumor, although other solid tumors may be found [112]. Sensory-motor neuropathy is a quite common paraneoplastic feature in patients with onconeural antibodies, especially Hu and CRMP-5 antibodies. The CRMP-5 antibody is particularly associated with SCLC and thymoma [30]. The CRMP-5 antibody binds to oligodendrocytes as well as to neurons in specific brain regions and the retina and Schwann cells of the peripheral nervous system. In accordance with this, the clinical characteristics are heterogeneous. Many patients exhibit mixed axonal and demye-linating sensory-motor neuropathy, optic neuritis, or cerebellar dysfynction [85, 113], as well as extrapyramidal symptoms (Chapter 5.3). 

The prevalence and impact of vitamin B12 deficiency vary in different groups, races, and geographic areas (Stabler and Allen, 2004). In North America, true autoimmune PA is uncommon, far less common than vitamin B12 deficiency as a whole, especially in the elderly population. Older studies, mainly from Scandinavia, indicated a prevalence of PA in the population of 0.1%-0.2%, but a study of people over 60 years of age in Los Angeles found 2.3% of subjects affected, of whom most (1.9%) were undiagnosed (Carmel, 1996). The prevalence of undiagnosed PA was 2.7% in women and 1.4% in men the rates were 4.3% in black women, 4.0% in white women, but lower in women of other races. These figures refer to patients who had characteristic antibody profiles and whose disorder corrected with administration of IF. Vitamin B12 deficiency per se was not assessed (Carmel, 1996). Other studies in subjects over... 

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