• β₂ glycoprotein I
• anticardiolipin antibodies
• systemic sclerosis

Systemic sclerosis (SSc) is a multisystem disease in which organ damage is characterised by fibrosis, microvascular occlusion, and proliferation of the vascular intima. The reported prevalence of anticardiolipin antibodies (aCL) in SSc varies from 0 to 25%,^1–7 and reports of clinical associations have been variable.^3,4,6,7 To our knowledge, only one study has examined antibodies to β₂ glycoprotein I (aβ₂GPI) in SSc and shown a correlation with pulmonary hypertension and raised mean pulmonary artery pressure.⁸ In our study we examined the frequency of aβ₂GPI and aCL in SSc and Raynaud's phenomenon (RP).

Twenty six patients with SSc (16 diffuse, 10 limited), 23 with RP, and 21 healthy volunteers (employees at the research facility) were included in this retrospective study. Informed consent was obtained. All 16 patients with diffuse SSc and one patient with limited SSc patients met American Rheumatism Association (ARA) preliminary criteria for scleroderma.⁹ The remaining nine with limited SSc had at least three of the following: sclerodactyly, calcinosis, Raynaud's phenomenon, oesophageal dysmotility, telangiectasia, or positive anticentromere antibodies. The patients with RP had no manifestations of connective tissue disease. Clinical and laboratory assessments were recorded at the initial visit.

aβ₂GPI and aCL were measured by enzyme linked immunosorbent assay (ELISA; INOVA Diagnostics, Inc, San Diego, CA and Hemagen Diagnostics, Inc Waltham, MA, respectively). Commercially obtained HEp-2 slides (Immuno Concepts, Sacramento, CA) were used for indirect immunofluorescence (IIF). Samples were tested for antibodies to topoisomerase I (Scl-70), U1 ribonucleoprotein (U1-RNP), and Sjögren's syndrome antigens A and B (SS-A/SS-B) by double immunodiffusion.

Student's t test (two tailed) was used for comparison of means, and Fisher's exact test (two tailed) for analysis of frequencies. Age distributions were compared with the Mann-Whitney test because healthy controls described their age in decades, not years.

Table 1 summarises the demographics and laboratory data for the study group. The patients with SSc were significantly older than both the healthy controls (p=0.005) and the patients with RP (p=0.02). All mean laboratory values were within the normal range. Figure 1 compares the values for tests among the study groups except aβ₂GPI IgG, where all tests were negative. IgM aβ₂GPI were found in two patients with SSc (8%), one patient with RP (4%), and none of the healthy controls (p>0.05). Three (12%) patients with SSc, five (22%) with RP, and one (5%) of the healthy controls had positive tests for IgG or IgM anticardiolipin (p>0.05). The sera positive for aCL were not the same as those positive for aβ₂GPI.

The two patients with SSc positive for aβ₂GPI had mean disease duration of 19 months; both had cutaneous manifestations and one had hypoxia with decreased carbon monoxide transfer factor (Tlco). The three patients with SSc and aCL had mean disease duration of 112 months. One had hypoxia (with normal Tlco and non-restrictive pulmonary function tests), one had restrictive lung disease and digital ulcers, and one had oesophageal hypomotility. None of the study participants had thrombocytopenia or a history of deep venous thrombosis. Twenty two per cent of the group with Raynaud's disease had aCL, which is higher than the 8.7% reported by Vayssairat et al.¹⁰ Patients with positive tests did not differ from those who had negative clinical manifestations or laboratory values.

All of the patients with SSc and RP and 13% of the healthy controls had positive IIF tests on HEp-2 substrates. None of the patients with SSc had antibodies to topoisomerase I (Scl-70) or SS-A/SS-B. No IIF pattern correlated with aβ₂GPI or aCL.

In our study we found that the frequency of antibodies to β₂GPI and aCL was low in scleroderma, 8% and 12% respectively. There were no clear clinical or laboratory correlations with a positive test.

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Figure 1

Comparison of aβ₂GPI and aCL antibody levels in patients with SSc, RP, and normal controls. The numbers on the ordinate represent optical density values converted to SMU (standard IgM β₂GPI units), MPL (1 MPL unit = the binding of 1 μg/mL IgM aCL), or GPL (1 GPL unit=the binding of 1 μg/ml IgG aCL). The arrows indicate the cut off values for each dataset.