Immune responses in monkeys to lenses from patients with contact lens induced giant papillary conjunctivitis.

The clinicopathologic findings in contact lens-induced giant papillary conjunctivitis (GPC) suggest that the syndrome is the result of a complex immunological process, an idea supported by the presence of elevated tear concentrations of IgG and IgE in GPC. Several groups of investigators have proposed that GPC may be due, in part, to the coating of the contact lens. To test this hypothesis we undertook development of an animal model of GPC in cynomolgus monkeys. Two soft contact lenses from patients with GPC, two from asymptomatic contact lens wearers, and two clean, unused lenses were each placed in one eye and held in place with a partial tarsorrhaphy. Tears from the two monkeys with GPC lenses showed increased levels of IgG (43 +/- 10 micrograms/mL), IgA (54.3 +/- 12.8 micrograms/mL) and IgE (7.7 +/- 3.3 IU/mL) 35-75 days post-lens placement. While the tears from the two monkeys with clean lenses, and the two monkeys with lenses from asymptomatic contact lens wearers had elevated levels of IgG compared to the contralateral control eye without a lens, the tear IgE levels remained normal. Histopathology studies of tarsal conjunctival biopsy material from the monkeys with GPC lenses showed an intense round cell infiltrate at the epithelial-stromal junction. Mast cells were seen in the epithelial layers. These studies suggest that some factor (or factors) in the lens coating from GPC patients was able to induce a local tear IgE response and histopathological changes in monkeys. These changes are similar to the histopathological and immunological findings in human patients with GPC.

Tear lysozyme and lactoferrin levels in giant papillary conjunctivitis and vernal conjunctivitis.

We measured tear lysozyme by a radial immunodiffusion assay in patients with contact lens induced giant papillary conjunctivitis (GPC) and in patients with vernal conjunctivitis (VC). The VC and GPC patients had normal levels of tear lysozyme when compared to control individuals who did not have eye disease and to normal individuals who wore contact lenses without difficulty. In contrast, the tear concentration of lactoferrin (another important tear protein produced by the lacrimal glands) was reduced both in VC and GPC patients. Normal levels of tear lysozyme in the presence of reduced tear concentrations of lactoferrin may be a unique pattern in these two ocular conditions. The reduced tear levels of lactoferrin are probably not related to lacrimal gland dysfunction but to other factor(s) important in the pathogenesis of these two ocular disorders.

Tear lactoferrin levels in patients with external inflammatory ocular disease.

Lactoferrin, an iron complexing protein in normal tears, is an important component of the nonspecific host defense system of the external eye. We measured tear lactoferrin levels in patients with contact lens-induced giant papillary conjunctivitis (GPC) by an enzyme-linked immunosorbent assay (ELISA). Patients with active GPC (N = 26) had significantly reduced tear levels of lactoferrin (0.876 +/- 0.42 mg/ml) compared with normal individuals (N = 12; 1.73 +/- 0.46 mg/ml, P less than 0.0003) and the control contact lens wearers' group (N = 11; 1.57 +/- 0.92 mg/ml, P less than 0.003). Patients with vernal conjunctivitis (N = 10), an ocular disease with similar histopathology, had slightly reduced concentrations of tear lactoferrin (1.22 +/- 0.59 mg/ml). Patients with inactive GPC (N = 7) had normal tear levels of lactoferrin (1.33 +/- 0.49 mg/ml). The lactoferrin to total protein ratio in the tears was significantly reduced in patients with GPC compared to normal subjects, control contact lens wearers, and patients with inactive GPC. The decreased tear levels of lactoferrin in patients with GPC may contribute to increased coating of lenses with bacteria and their products and enhanced ocular inflammation which may play a role in the pathogenesis of GPC.

Cell-mediated immunity in cat-scratch disease.

The importance of cell-mediated immunity in cat-scratch disease (CSD) is suggested by the positive skin test reactions and granulomatous histopathology noted in patients with this disease. However, an earlier investigation found that lymphocytes from patients with CSD and control subjects were equally unresponsive in vitro to cat-scratch antigen. In contrast, we found that 16 patients with CSD had significantly increased lymphocyte transformation responses to cat-scratch antigen when patients were compared to control subjects. This cell-mediated immune response may be directed against nonviable bacteria in the involved lymph nodes and may be the major mechanism responsible for the granulomatous reaction and clinical features of CSD.

Pollen-specific IgG antibodies in the tears of patients with allergic-like conjunctivitis.

Specific-IgG antibodies to rye grass and/or AgE in the tear secretions were demonstrated in studies of patients with the clinical features of allergic conjunctivitis but negative immediate skin reactivity and absent IgE antibodies by RAST to the inhalant pollen allergens. Studies by use of transferrin as a marker for the vascular leakage of plasma proteins into the tear secretions indicated that more than 98% of these pollen-specific IgG antibodies were locally produced by the conjunctival tissues of the external eye. These findings suggest that IgG-mediated immune mechanism(s) are important in the pathogenesis of some patients with allergic-like conjunctivitis.

IgG specific antibodies to rye grass and ragweed pollen antigens in the tear secretions of patients with vernal conjunctivitis.

We studied the tears of 30 patients (25 males and five females, ranging in age from 8 to 34 years) with vernal conjunctivitis for pollen-specific IgG antibodies to rye grass and ragweed antigen E by an enzyme-linked immunosorbent assay (ELISA). Eighteen of 30 (60%) and 20 of 30 (67%) patients with vernal conjunctivitis had significant levels (more than 2 S.D. from the mean of control tears) of IgG antibodies in their tear secretions to rye grass (geometric mean = 68.7 ELISA units) and ragweed antigen E (geometric mean = 50 ELISA units), respectively. In contrast, the control groups (eight atopic individuals, four with seasonal rhinitis, and 12 with allergic conjunctivitis) had low amounts of specific IgG antibodies to these two pollen antigens in their tears. Total IgG and IgM were also increased in the tears of patients with vernal conjunctivitis. To evaluate whether these immunoglobulins and specific IgG antibodies were locally produced by the conjunctival tissues, we used transferrin as a marker for the leakage of plasma proteins into tears. We found that the specific IgG antibodies to rye grass or ragweed antigen E, or both, in the tears were locally produced by the conjunctival tissues. The local production ranged from 20% to 99.9%. Of 17 patients with vernal conjunctivitis and undetectable pollen-specific IgE antibodies in their tears, 14 (82.4%) had tear specific IgG antibodies to rye grass or ragweed antigen E or both, whereas of those with measurable tear IgE antibodies, only nine of 13 (69%) had tear IgG antibodies to rye grass or antigen E or both. These results suggested that both IgE- and IgG-mediated immune mechanisms may be important in the pathogenesis of vernal conjunctivitis.