HLA-DQw Alloantigens and Pulmonary Dysfunction in Rheumatoid Arthritis: Pulmonary FunctionPulmonary Function
Table 4 demonstrates the data on pulmonary function classified by the major DQw phenotypes. DQwl-positive patients had evidence of a restrictive ventilatory defect with a lower percentage of predicted FEVX, FVC, and D than DQwl-negative patients. DQw3-positive patients had evidence of an obstructive ventilatory defect with a lower FEVj/FVC than DQw3-negative patients. The TLC, functional residual capacity (FRC), and RV were not significantly different between any HLA-DQw allelic subgroup. The presence of DQw2 seemed to be “protective” in that the percent predicted FEVi and FVC were significantly higher in the population of DQw2-positive patients.

Analysis of variance for independent and interactive effects of these DQw alleles showed a significant independent effect of DQwl on FVC (p<0.05), FEVX (p<0.05), and D (p<0.05). DQw3 and the interaction of DQwl and DQw3 had borderline but not significant effects on FEV^FVC (p = 0.08 and p = 0.10, respectively).
When obstructive pulmonary disease was defined as the presence of FE\VFVC less than 70 percent of predicted, there was an increased frequency of obstructive pulmonary disease among the DQwl/DQw3 phenotypic patients; five (29 percent) of 17 DQwl/ DQw3-positive patients had obstructive disease of the airways, compared to only two (7 percent) of the remaining 30 DQl/DQ3-negative patients (p = 0.05). Table 5 shows the pulmonary function data of DQwl/ DQw3 heterozygous subjects compared to the other subjects grouped by smoking status. The presence of airflow obstruction appeared to be confined only to the smoking population.
The stepwise regression analysis of all potential predictors of pulmonary function demonstrated that an abnormal FVC and D were best predicted by the presence of the DQwl allele. A low FEVL was best predicted by the DQwl/DQw3 phenotype. Sex, race, smoking status, DR4, and latex titer did not significantly improve the ability to predict abnormal pulmonary function. Keratoconjunctivitis sicca was a strong predictor of an abnormal FEVj/FVC, and a high ESR predicted both low FEVX and FVC (Table 6). The results of mean pulmonary function for each phenotype is shown in Table 7.
Table 4—Data on Pulmonary Function

HLA Status No. of Patients Percent of Predicted FEV1/FVC%
FEVi FVC D TLC FRC RV
DQ1 positive 30 84.2± 19.8$ 88.0± 17.9$ 85.6±20.9§ 91.3± 14.6 84.6 ±23.1 92.9 ±30.1 77.2 ±6.0
DQ1 negative 17 95.8 ±13.6$ 99.1 ±12.2$ 101.9±24.5§ 94.6 ±12.4 73.6±23.2 85.7 ±27.8 76.9 ±9.6
DQ2 positive 16 96.4 ±13.4+ 98.5 ± 13.8|| 92.4±21.8 95.6 ±13.2 84.7±21.8 91.9± 14.4 79.3±5.4
DQ2 negative 31 84.3 ± 19.6+ 88.7± 17.5|| 91.0±24.5 90.9 ±14.1 78.6 ±24.3 89.5 ±32.6 75.8 ±9.4
DQ3 positive 30 86.4 ±20.2 91.5± 17.1 93.8 ±23.1 93.6 ±12.1 78.8 ±24.6 92.7 ±30.3 75.0 ±9.2$
DQ3 negative 17 91.9± 15.1 92.9± 16.8 87.4 ±24.1 90.5 ±16.7 83.9±21.7 86.1 ±22.4 80.4 ±5.6$

Table 5—Data on Pulmonary Function

Group No. of Patients Percent of Predicted
FEVj FVC TLC RV D FE\7FVC%
All subjects
DQ1/DQ3 positive 17 78.9 ± 22.lt 86.3± 18.6 94.2± 13.7 100.9±33.4 87.1 ±23.0 73.2± 10.8$
DQ1/DQ3 negative 30 93.3 ±14.3+ 95.3 ±15.1 91.6± 14.1 84.4 ±22.4 94.0 ±23.3 79.1± 5.9*
Smokers
DQ1/DQ3 positive 13 80.1 ±24.4$ 88.4±20.2 98.4± 11.3 106.2±36.0 89.5 ±26.1 71.2± 11.2$
DQ1/DQ3 negative 18 95.7 ± 12.lt 98.4± 12.0 93.8± 14.2 86.0±21.5 92.2 ±28.3 78.7 ±7.6$
Nonsmokers
DQ1/DQ3 positive 4 78.7 ±14.9 79.3± 11.4 80.7 ±13.0 83.8± 15.9 79.1 ±10.7 79.8±6.6
DQ1/DQ3 negative 12 89.8± 17.1 90.6± 18.4 88.2± 13.7 81.9±23.9 96.8± 13.6 79.7±4.7

Table 6—Stepwise Regression Analysis

DependentVariables Predictors
No.l No. 2 No. 3
FEVi DQ1/DQ3 t= -2.66 ESR t= -2.14
FVC DQ1 t= —3.55 ESR t= -3.17 DQ1/DQ2 t= +2.47
DCO DQ1 t= -2.15
FEVj/FVC KCS* t= -2.73

Table 7—Pulmonary Function according to HLA-DQ Allelic Combinations

AllelicCombinations No. of Patients Percent of Predicted FEVJFVC%
FEVi FVC D
DQ1/DQ- present 5 78.8± 11.6 78.8 ±14.1 80.4 ±25.1 81.6±5.7
DQ1/DQ- absent 42 89.5± 18.9 93.6 ±16.5 92.8 ±23.1 76.4 ± 8.5
DQ2/DQ- present 4 97.6 ±15.1 101.4± 13.5 99.5 ±39.8 76.6±7.1
DQ2/DQ- absent 43 87.6± 18.7 91.2± 17.0 90.7±21.9 77.0±8.6
DQ3/DQ- present 9 95.9 ±13.6 98.8 ±12.6 104.4 ±22.9 77.4±6.8
DQ3/DQ- absent 38 86.6± 19.2 90.4± 17.4 88.4 ±22.7 76.9±8.8
DQ1/DQ2 present 8 97.1 ±13.1 97.4 ±15.8 85.7± 12.6 81.6±4.4*
DQ1/DQ2 absent 39 86.6± 19.1 90.9± 17.0 92.7 ±25.0 76.0 ±8.7*
DQ1/DQ3 present 17 79.8 ±22.1+ 86.3± 18.6 87.1 ±23.5 -H-OO

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DQ1/DQ3 absent 30 93.3 ± 14.3t 95.3 ±15.1 94.01 ±23.3 79.1 ±5.9t
DQ2/DQ3 present 4 93.6± 15.9 97.5± 13.4 98.5± 13.6 77.3±4.7
DQ2/DQ3 absent 43 87.9± 18.8 91.5± 17.1 90.8 ±24.1 76.9±8.7