Serological Influences on Dry Eye: Insights from the Sjögren's International Collaborative Clinical Alliance

To define associations between serologies, specifically Sjögren syndrome-related antigen A (SSA) antibody and immunoglobulin (Ig) levels, on ocular profiles in patients enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) cohort.

A retrospective cohort study.

Individuals from the SICCA cohort (n = 3514).

A retrospective analysis to examine relationships between dry eye (DE) symptoms and signs and serologic status, including SSA (SSA+ Sjögren disease [SjD], SSA- SjD, non-SjD) and Ig (G, A, M) levels (low, normal, and high).

Univariate analyses using analysis of variance and chi-square tests examined differences in ocular profiles by serologies. Multivariable analyses were then performed to account for potential confounding variables, including other serological measures.

The mean age of the SICCA cohort was 53 ± 13 years, with the majority identifying as female (91%, n = 3185) and White (54%, n = 1894). The presence of SSA impacted ocular profiles, with the SSA+ SjD group reporting less severe symptoms compared with the SSA- SjD and non-SjD groups (spontaneous pain: 2.61 ± 2.83 vs. 3.39 ± 3.01 vs. 3.52 ± 3.09, P < 0.001), but more frequently having ocular signs (low tear production: 57% vs. 52% vs. 28%, P < 0.001; ocular surface staining [OSS]: 83% vs. 69% vs. 35%, P < 0.001). Immunoglobulin levels showed a similar pattern, with the high IgG level group reporting less severe ocular symptoms in the SjD (spontaneous pain: 2.41 ± 2.82 vs. 3.10 ± 2.91 vs. 3.40 ± 2.96; P < 0.001 and P < 0.05) and non-SjD (spontaneous pain: 2.09 ± 2.35 vs. 3.58 ± 3.11 vs. 3.85 ± 3.11; P < 0.001) groups but more severe signs (SjD group: low tear production: 60% vs. 53% vs. 49%; OSS: 88% vs. 72% vs. 70%; P < 0.001) compared with the normal and low-level groups. A similar pattern was noted for IgA levels. Most associations remained significant when considered concomitantly.

Ocular manifestations of DE are influenced by serological factors. Specifically, SSA+ and high IgG and IgA status align with a disease picture of clinical signs of DE disease out of proportion to pain symptoms, while SSA- and low and normal IgG and IgA status align with a DE disease picture of symptoms that outweigh signs.

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