Anti-cortactin autoantibodies are associated with key clinical features in adult myositis but are rarely present in juvenile myositis.

Abstract

Objective:

To define the prevalence and clinical phenotype of anti-cortactin autoantibodies in adult and juvenile myositis.

Methods:

In this longitudinal cohort study, anti-cortactin autoantibody titers were assessed by ELISA in 670 adults and 343 juvenile myositis patients as well as 202 adult and 90 juvenile healthy controls. The prevalence of anti-cortactin autoantibodies was compared among groups. The clinical features of patients with and without anti-cortactin autoantibodies were also compared.

Results:

Anti-cortactin autoantibodies were more common in adult dermatomyositis (DM) patients (15%, p=0.005), particularly those with co-existing anti-Mi-2 (24%, p=0.03) or anti-NXP2 (23%, p=0.04) autoantibodies. In adult myositis, anti-cortactin was associated with DM skin involvement (62% vs. 38%, p=0.03), dysphagia (36% vs. 17%, p=0.02) and co-existing anti-Ro52 (47% vs. 26%, p=0.001) or anti-NT5C1a autoantibodies (59% vs. 33%, p=0.001). Moreover, the titers of anti-cortactin antibodies were higher in patients with interstitial lung disease (0.15 vs. 0.12 arbitrary units, p=0.03). The prevalence of anti-cortactin autoantibodies was no different in juvenile myositis (2%) or any juvenile myositis subgroup compared to juvenile healthy controls (4%). Nonetheless, juvenile myositis patients with these autoantibodies had a higher prevalence of mechanic’s hands (25% vs. 7%; p=0.03), a higher number of hospitalizations (2.9 vs. 1.3, p=0.04), and lower peak CK values (368 vs. 818 IU/L, p=0.02)

Conclusions:

The prevalence of anti-cortactin autoantibodies is increased in adult DM patients with co-existing anti-Mi-2 or anti-NXP2 autoantibodies. In adults, anti-cortactin autoantibodies are associated with dysphagia and interstitial lung disease.

INTRODUCTION

The inflammatory myopathies (IIM) are a heterogeneous group of diseases and patients may be classified as having dermatomyositis (DM), polymyositis (PM), immune-mediated necrotizing myopathy (IMNM), or overlap myositis (OM) based on clinical and muscle biopsy features.(1) In older adults, inclusion body myositis (IBM) represents another important type of IIM.(2) In addition to these clinicopathological categories, myositis-specific autoantibodies (MSAs) define distinct subtypes of myositis with unique clinical features. Furthermore, many myositis patients have myositis-associated autoantibodies (MAAs) that may be found in patients with other autoimmune disorders as well.(3)

In 2014, autoantibodies targeting cortactin, a ubiquitous cytoplasmic protein that regulates polymerization of the actin cytoskeleton, were identified in adult patients with myositis(4) and myasthenia gravis(5). In a Spanish cohort of 162 adult myositis patients, these MAAs were present in 7 of 34 (20%) PM, 9 of 117 (7.6%) DM, 2 of 7 (28%) IMNM, and 0 of 4 (0%) IBM patients.(4) Moreover only 1 of 29 patients with non-inflammatory myopathies were detected as positive. Anti-cortactin autoantibodies were not associated with distinct clinical features in this relatively small cohort of myositis patients.(4) Furthermore, the prevalence and clinical features of anti-cortactin autoantibodies in juvenile myositis have not been described.

The objective of the current study was to define the prevalence and clinical characteristics of adult and pediatric myositis patients with anti-cortactin autoantibodies. To accomplish this, we utilized large cohorts of well-characterized adult and juvenile myositis patients that included significant numbers of patients with each of the major MSA-defined subtypes of myositis.

MATERIALS AND METHODS

Adult patients and sera

Six hundred and seventy patients enrolled in the Johns Hopkins Myositis Center Longitudinal Cohort study between 2002 to 2015 were included in the study. These patients were classified as having IBM if they fulfilled Lloyd-Greenberg criteria,(6) DM or PM according to Bohan and Peter’s criteria,(7) or clinical amyopathic dermatomyositis (CADM) according to Sontheimer’s criteria.(8) The clinical features of anti-cortactin positive patients were compared to anti-cortactin negative patients in the subset of 409 patients that had IBM or were positive for autoantibodies recognizing Mi-2, NXP2, TIF1γ, MDA5, Jo1, SRP, or HMGCR by at least two immunologic techniques from among the following: ELISA, in vitro transcription and translation followed by immunoprecipitation, line blotting (EUROLINE myositis profile), or immunoprecipitation from S35-labeled HeLa cell lysates.(9, 10) The demographics, clinical and laboratory features were collected prospectively at each visit. Dysphagia was defined by patient report as any type of difficulty swallowing, and interstitial lung disease (ILD) was defined through a multidisciplinary approach as suggested by the American Thoracic Society.(11) Sera samples from 202 healthy control adults donors to the NIH blood bank were also included in the study.

Juvenile patients and sera

Three-hundred forty-three patients from the Childhood Myositis Heterogeneity Collaborative Study (12) (13) enrolled in National Institutes of Health studies between 1989 and 2016 with probable or definite juvenile-onset myositis by Bohan and Peter criteria(7) were included. Sera from 90 healthy control children enrolled in the same studies were available. A physician questionnaire captured demographics, clinical and laboratory features, as well as therapeutic usage.(13) Patient sera from the time of enrollment were tested for myositis autoantibodies by validated methods, including protein and RNA immunoprecipitation (IP) using radiolabeled HeLa or K562 cell extracts, double immunodiffusion, immunoblot, or ELISA.(13-15) For anti-TIF1g, anti-MJ, and anti-MDA5 autoantibodies, serum samples were screened by IP, with confirmation testing by IP-blotting.(16)

Anti-cortactin autoantibody testing

For the anti-cortactin autoantibody ELISA, the earliest available serum sample for each patient was used. 96-well ELISA plates were coated overnight at 4°C with 100ng of recombinant cortactin protein (OriGene, TP710315) diluted in PBS. After washing the plates, human serum samples, diluted 1:100 in PBS with 5% non-fat milk and 0.05% Tween (PBS-T), were added to wells (1 hour at room temperature). After washing, the HRP-labeled goat anti-human antibody (Jackson ImmunoResearch 109-036-088; 1:10,000) was added to each well (40 minutes at room temperature). Color development was performed using SureBlue™ peroxidase reagent (KPL) and absorbances at 450 nm were determined. Test sample absorbances were normalized to the sera of an arbitrary positive anti-cortactin patient, a reference serum included in every ELISA. The cutoff (0.21 arbitrary units [AU]) for a normal anti-cortactin autoantibody titer was defined as the mean (0.078 AU) plus two standard deviations (2 x 0.067 AU) of the normalized absorbances of the 90 healthy children control subjects. This cutoff was determined to be optimal based on a graphical analysis of the curve of normalized absorbances (Supplementary Figure 1).(17)

Standard protocol approvals and patient consents.

This study was approved by the Johns Hopkins and National Institutes of Health Institutional Review Boards; written informed consent was obtained from each participant.

Analysis

Dichotomous variables were expressed as absolute frequencies and percentages, and continuous variables were reported as means and standard deviations. Bootstrapping with 1000 replicates using the first-order normal approximation was used to statistically validate our key estimates using using the boot R library v.1.3 for dichotomous variables and Stata’s command bootstrap for continuous variables; these results and are provided as 95% confidence intervals (CI). Comparisons between groups were made using Chi-squared, Fisher’s exact tests, or Student’s t-test. Logistic and linear regression was used to adjust comparisons for the length of follow-up, and MSAs (or MSAs + IBM in adult patients). As previously described, indirect standardization was used to calculate the mortality (standardized mortality rate [SMR]) and rate of cancer (standardized cancer rate [SMR]) compared to the general population in adult myositis patients.(10) Statistical analyses were performed using Stata/MP 14.1 and R v. 4.0.3. A two-sided P value of <0.05 was considered significant with no correction for multiple comparisons.

RESULTS

Prevalence of anti-cortactin autoantibodies in adult myositis patients

Overall, the prevalence of anti-cortactin autoantibodies in the 670 adult myositis patients was no different than their prevalence in 202 adult healthy controls (11% [95%CI 9-13%] vs. 8% [95%CI 4-11%]; p=0.2). However, anti-cortactin autoantibodies were more prevalent among adult DM patients compared to either healthy adults (15% [95%CI 11-19%] vs. 8% [95%CI 4-11%]; p=0.02) or to the combined group of non-DM adult myositis patients (15% [95%CI 11-19%] vs. 8% [95%CI 6-11%]; p=0.005). Among the autoantibody-defined adult DM patients, the anti-Mi-2-positive and anti-NXP2-positive patients were the only two groups with a higher prevalence of anti-cortactin autoantibodies compared to adult healthy controls (24% [95%CI 8-40%] vs. 8% [95%CI 4-11%] and 23% [95%CI 9-36%] vs. 8% [95%CI 4-11%], respectively; both p=0.01). Although the prevalence of anti-cortactin autoantibodies was lower in IBM patients (4% [95%CI 1-7%]; p=0.002) and the anti-HMGCR autoantibody-defined subgroup (3% [95%CI 0-8%]; p=0.05) than in other myositis patients, anti-cortactin autoantibodies were not significantly decreased in these two groups compared to the adult healthy controls (Table 1, Supplementary Figure 2). Anti-cortactin antibodies were also found in 18% [95%CI 3-33%] of 28 anti-Pm/Scl, and 22% [95%CI 0-50%] of 9 anti-U1RNP patients tested. There was an increased level of muscle weakness in the arm abductors of anti-cortactin-positive patients with anti-Pm/Scl autoantibodies, but the rest of the clinical features were similar for anti-Pm/Scl and anti-Ku antibodies.

Table 1.

Prevalence of anti-cortactin autoantibodies in adult and juvenile myositis patients.

Adult myositis					Juvenile myositis
	% (n/total)	p-value vs. other myositis patients	p-value vs. healthy controls			% (n/total)	p-value vs. other myositis patients	p-value vs. healthy controls
Clinical groups					Clinical groups
Dermatomyositis	15% (42/279)	0.005	0.02		Dermatomyositis	3% (8/282)	NS	NS
CADM	19% (4/21)	NS	NS		Polymyositis	0% (0/23)	NS	NS
Polymyositis	10% (23/231)	NS	NS		Overlap myositis	0% (0/38)	NS	NS
IBM	4% (5/139)	0.002	NS		Autoantibody group
Autoantibody group					Anti-Mi-2	7% (1/15)	NS	NS
Anti-Mi-2	24% (7/29)	0.03	0.01		Anti-NXP2	5% (4/83)	NS	NS
Anti-NXP2	23% (8/35)	0.04	0.01		Anti-TIF1g	2% (2/124)	NS	NS
Anti-TIF1g	13% (6/46)	NS	NS		Anti-MDA5	0% (0/28)	NS	NS
Anti-MDA5	16% (4/25)	NS	NS		Anti-Jo1	17% (1/6)	NS	NS
Anti-Jo1	10% (5/49)	NS	NS		Anti-SRP	0% (0/6)	NS	NS
Anti-SRP	19% (5/27)	NS	NS		Anti-HMGCR	0% (0/3)	NS	NS
Anti-HMGCR	3% (2/59)	0.05	NS		Total	2% (8/343)
Total	11% (74/670)

NS: nonsignificant. Chi-squared or Fisher’s exact tests were used for the univariate comparisons. CADM: adult clinically amyopathic dermatomyositis; IBM: inclusion body myositis.

The epidemiological features were similar between groups, except for a lower prevalence of anti-cortactin antibodies in white adult myositis patients (59% [95%CI 48-71%] vs. 75% [95%CI 72-78%]; 0.02) (Table 2).

Table 2.

Myositis-associated autoantibody (MAA) status, epidemiologic, and clinical features of anti-cortactin autoantibodies in adult and juvenile myositis patients.

	Adult myositis				Juvenile myositis
	Anti-CTTN+ (n=74)	Anti-CTTN− (n=596)	Univariate p-value	Multivariate p-value	Anti-CTTN+ (n=8)	Anti-CTTN− (n=335)	Univariate p-value	Multivariate p-value
Epidemiologic features and MAA
Female sex	72% (53)	62% (369)	NS	NS	62% (5/8)	71% (238)	NS	NS
Race
White	59% (44)	75% (447)	0.004	0.02	75% (6)	64% (215)	NS	NS
Black	27% (20)	17% (99)	0.03	NS	13% (1)	16% (53)	NS	NS
Other races	14% (10)	8% (50)	NS	NS	13% (1)	20% (67)	NS	NS
Age of onset (years)	45.8 (14.6)	50.5 (14.7)	0.01	NS	10.8 (5.5)	8.9 (4.2)	NS	NS
Time of follow-up (years)	2.8 (3.3)	2.8 (3.3)	NS	NS	5.2 (4.8)	6.1 (7.2)	NS	NS
Cancer associated myositis	7% (5)	12% (67)	NS	NS	0% (0)	0% (0)	NS	NS
Death during follow-up	0% (0)	5% (27)	NS	NS	0% (0)	4% (12)	NS	NS
Myositis-associated autoantibodies *
Anti-Ro52	47% (35)	26% (156)	< 0.001	0.001	0% (0)	16% (50)	NS	NS
Anti-NT5c1a	59% (10)	33% (70)	0.03	0.001	25% (2)	28% (86)	NS	NS
Clinical features	(n=42)	(n=367)			(n=8)	(n=335)
Muscle weakness	95% (40)	96% (354)	NS	NS	100% (8)	99% (333)	NS	NS
Skin involvement
DM-specific skin involvement	62% (26)	38% (141)	0.003	0.03	100% (8)	91% (305)	NS	NS
Raynaud's phenomenon	21% (9)	14% (51)	NS	NS	25% (2)	14% (48)	NS	NS
Mechanic's hands	19% (8)	18% (66)	NS	NS	25% (2)	7% (24)	NS	0.03
Calcinosis	12% (5)	10% (36)	NS	NS	50% (4)	29% (98)	NS	NS
Interstitial lung disease	24% (10)	16% (58)	NS	NS	12% (1)	9% (30)	NS	NS
Esophageal involvement
Dysphagia	36% (15)	17% (61)	0.003	0.02	50% (4)	41% (137)	NS	NS
Gastroesophageal reflux disease	67% (28)	47% (174)	0.02	0.02	12% (1)	22% (73)	NS	NS
Arthritis	17% (7)	16% (60)	NS	NS	50% (4)	52% (173)	NS	NS
Fever	19% (8)	9% (33)	0.05	NS	14% (1)	30% (101)	NS	NS

Dichotomous variables were expressed as a percentage (count) and continuous variables as mean (SD). Univariate comparisons of continuous variables were made using Student’s t-test while dichotomous variables were compared either using the chi-squared test or Fisher’s exact test, as appropriate. Multivariate comparisons were performed using linear regression for continuous variables and logistic regression for dichotomous variables. All multivariate comparisons were adjusted by the patient group (IBM or autoantibody group) for the epidemiological comparisons and by time of follow-up, and patient group for the comparisons of clinical features. DM-specific skin involvement: either heliotrope, Gottron’s sign, or papules.

^*Anti-NT5c1a autoantibodies in adults were performed only in a subset of 227 patients (mostly IBM [n=139] and DM [n=50]). In children, both anti-Ro52 and anti-NT5c1a were performed in 314 of the total number of patients.

Clinical features of anti-cortactin autoantibodies in adult myositis patients

To determine whether anti-cortactin autoantibodies are associated with specific clinical features, we first performed a multivariate analysis comparing those with and without these autoantibodies while controlling for follow-up time and patient group (Table 2). This revealed an increased prevalence of dysphagia and gastroesophageal reflux among all anti-cortactin-positive compared to anti-cortactin-negative patients (36% [95%CI 21-50%] vs. 17% [95%CI 13-20%] and 67% [95%CI 52-81%] vs. 47% [95%CI 42-52%], respectively; both p=0.02; Table 2). Of note, dysphagia was substantially more common in anti-Mi-2-positive patients with anti-cortactin autoantibodies than in anti-Mi-2-positive patients without anti-cortactin autoantibodies (100% vs. 41% [95%CI 20-62%]; p=0.008). Interestingly, the MAAs anti-Ro52 (47% [95%CI 36-59%] vs. 26% [95%CI 23-30%]; p=0.001) and anti-NT5C1a (59% [95%CI 35-82%] vs. 33% [95%CI 27-40%]; p=0.001) were more likely to be present in the sera of adult myositis patients with anti-cortactin autoantibodies (Table 2). Among the 10 patients positive for both for anti-cortactin and anti-NT5c1a antibodies, 4 had IBM and 6 had DM. Of those 10 patients, 6 had dysphagia (4 DM).

Given their association with DM, there was an expected increased prevalence of DM-skin features in adult myositis patients with anti-cortactin autoantibodies (62% [95%CI 47-77%] vs. 38% [95%CI 33-43%]; p=0.03). Otherwise, the clinical features of adult myositis patients with and without anti-cortactin autoantibodies were remarkably similar (Table 2). For instance, there were no differences in the pattern or severity of weakness, muscle enzyme levels, the severity of lung disease, thigh MRI features, or treatments received (Supplementary Table 1-5). Furthermore, compared to the general population, there were no differences in the survival (SMR 0, 95%CI 0–2) or cancer rates (SCR 1.3, 95%CI 0.4 – 3) in anti-cortactin positive patients.

Next, we explored whether anti-cortactin autoantibody titers were associated with specific clinical features. The multivariate analysis comparing anti-cortactin autoantibody titers in patients with and without each clinical feature, while controlling for follow-up time and patient group, demonstrated that titers were higher in patients with DM-skin features (0.14 [95%CI 0.12-0.16] vs. 0.11 [95%CI 0.09-0.12], p=0.008) and dysphagia (0.14 [95%CI 0.12-0.16] vs. 0.11 [95%CI 0.1-0.12], p=0.005). Furthermore, patients with interstitial lung disease also had higher anti-cortactin autoantibody titers than those without interstitial lung disease (0.14 [95%CI 0.11-0.19] vs. 0.11 [95%CI 0.10-0.13], p=0.005) (Supplementary Table 6).

Of note, at the onset of the disease, the presence of dysphagia was also more prevalent in patients with anti-cortactin autoantibodies (29% [95%CI 15-42%] vs. 10% [95%CI 7-13%], p=0.01). Likewise, the presence of ILD at the onset of the disease showed a trend towards being more frequent in patients with anti-cortactin antibodies (10% [95%CI 1-18%] vs. 2% [95%CI 1-4%], p=0.06).

Prevalence and clinical features of anti-cortactin autoantibodies in juvenile myositis patients

Overall, anti-cortactin autoantibodies were not more prevalent in juvenile myositis patients compared to juvenile healthy control subjects (2% [95%CI 1-4%] vs. 4% [95%CI 0-9%]; p=0.3) (Table1). Of note, anti-cortactin antibodies were only found in patients with juvenile DM, which also accounted for the majority (82%) of the cohort. Unlike in adults, no differences were found in the prevalence of anti-cortactin autoantibodies among the different autoantibody-defined subgroups in juvenile myositis. Also, anti-cortactin antibodies were not found in any of the anti-Pm/Scl (n=13) or anti-U1RNP (n=24) patients tested. Except for a higher prevalence of mechanic’s hands (25% [95%CI 0-54%] vs. 7% [95%CI 4-10%]; p=0.03), a higher number of hospitalizations (2.9 [95%CI 0-6] vs. 1.3 [95%CI 1-1.5], p=0.04) and lower peak CK values (368 [95%CI 0-1800] vs. 818 [95%CI 534-1101], p=0.02), anti-cortactin autoantibody-positive juvenile myositis patients did not have any significant differences in terms of clinical features compared to anti-cortactin negative patients (Table 2 and Supplementary Table 7-8). Of note, juvenile myositis patients with mechanics hands had higher anti-cortactin autoantibody titers (0.1 [95%CI 0.05-0.14] vs. 0.07 [95%CI 0.07-0.08], p=0.04) (Supplementary Table 6). There were no differences in the disease course, mortality or treatments received (Supplementary Table 6-7).

DISCUSSION

In this study utilizing a large cohort of adult myositis patients, we demonstrate an increased prevalence of anti-cortactin autoantibodies in DM patients compared to those with PM, IBM, or adult healthy controls. Surprisingly, among all adult DM patients studied, only those with anti-Mi-2 or anti-NXP2 autoantibodies had an increased prevalence of anti-cortactin autoantibodies. Anti-cortactin antibodies would fall in the category of MAA since they were (1) previously found in myasthenia gravis,(5) (2) not associated with a specific myositis phenotype (e.g., dermatomyosits) but only with isolated clinical features, and (3) found in a significant proportion of normal individuals. To the best of our knowledge, anti-cortactin is the only MAA exclusively associated with MSA-defined DM subtypes.

We also found that anti-cortactin autoantibodies were strongly associated with dysphagia in adults. Since we previously demonstrated an increased risk of dysphagia in anti-NXP2-positive DM patients,(18) we considered the possibility that dysphagia could be more common in anti-cortactin-positive patients because of the high number of such patients with coexisting anti-NXP2 autoantibodies. However, dysphagia was associated with anti-cortactin autoantibodies even in a multivariate analysis controlling for myositis-specific autoantibodies, including anti-NXP2. We additionally found that adult myositis patients with interstitial lung disease also had higher titers of anti-cortactin autoantibodies than patients without this clinical feature.

Interestingly, anti-cortactin autoantibodies were not more common in any type of juvenile myositis compared to juvenile healthy controls. This makes anti-cortactin the only known MAA with an increased prevalence in adult, but not juvenile, forms of myositis. Nonetheless, anti-cortactin autoantibodies were still associated with increased prevalence of mechanic’s hands, a higher number of hospitalizations, and lower peak CK values in juvenile myositis patients. This observation suggests that anti-cortactin autoantibodies could still be associated with specific disease manifestations in children with myositis.

In the single prior report describing anti-cortactin autoantibodies in adult myositis,(4) this MAA was more common in PM than DM. Furthermore, no MSA or clinical features were found to be associated with anti-cortactin autoantibodies in the prior study. While we cannot fully account for these differences, we expect that by including more than four times as many adult myositis patients, the current study is more highly powered to accurately determine the prevalence of this MAA and any relevant clinical or serological associations. Future studies will be required to determine why the prevalence of anti-cortactin autoantibodies is only increased in adult DM patients with anti-NXP2 or anti-Mi-2 autoantibodies and why such patients have an increased risk of developing dysphagia.

Of note, anti-cortactin autoantibodies were more common in adult patients who were also positive for the myositis-associated autoantibodies anti-Ro52 and anti-NT5C1a. This suggests a potential association between the development of these three different myositis-associated autoantibodies. In this regard, it is of interest that anti-Ro52, anti-NT5C1a, and anti-cortactin autoantibodies each seem to be associated with more severe disease manifestations.(15, 19, 20) However, it remains to be determined whether the development of these MAAs contribute to more severe tissue damage or are simply the byproduct of a more robust immune response.

The current study has several limitations. First, most of the conclusions of this study are based on signs and symptoms that were recorded prospectively from natural history studies that have been ongoing since 2002 for adults and since 1989 for children. Consequently, we could not include classification strategies (e.g., the 2017 EULAR/ACR myositis classification scheme) or activity and damage tools that were not available when the studies started. Second, anti-cortactin antibodies were only tested by ELISA according to the original assay proposed by Labrador-Horrillo et al.(4) Finally, while most of the autoantibodies were systematically tested in all patients, only 227 of the adult patients were tested for anti-NT5c1a, and only 314 juvenile cases were tested for anti-Ro52 and anti-NT5c1a.

In conclusion, in this study we show that (1) the prevalence of anti-cortactin autoantibodies is increased in adult DM patients with co-existing anti-Mi-2 or anti-NXP2 autoantibodies, (2) in adults, anti-cortactin autoantibodies are associated with dysphagia and interstitial lung disease, and (3) anti-cortactin autoantibodies are associated with other myositis-associated autoantibodies, specifically anti-Ro52 and anti-NT5C1a, suggesting that the presence of these autoantibodies may be part of a broader, and largely uncharacterized, immunologic response in patients with myositis.

APPENDIX

ACKNOWLEDGMENTS:

To the Childhood Myositis Heterogeneity Collaborative Study Group^#

#. MEMBERS OF THE CHILDHOOD MYOSITIS HETEROGENEITY COLLABORATIVE STUDY GROUP WHO CONTRIBUTED TO THIS PROJECT:

Heinrike Schmeling, Bita Arabshahi, Imelda Balboni, Susan Ballinger, Lilliana Barillas-Arias, Mara Becker, Catherine April Bingham, John F. Bohnsack, Ruy Carrasco, Victoria Cartwright, Gail D. Cawkwell, Rodolfo Curiel, Jason Dare, Marietta M. DeGuzman, Kaleo Eade, Barbara Anne Ebernardt, Barbara S. Edelheit, Moussa El-Hallak, Terri H. Finkel, Stephen W. George, Ellen A. Goldmuntz, Beth Gottlieb, Brent Graham, William Hannan, Michael Henrickson, Gloria C. Higgins, Patricia Hobday, Alice Hoftman, Sandy Hong, Adam Huber, Lisa Imundo, Christi Inman, Anna Jansen, James Jarvis, Lawrence Jung, Philip Kahn, Ildy M. Katona, Yukiko Kimura, Daniel J. Kingsbury, W Patrick Knibbe, Bianca A. Lang, Maureen Leffler, Melissa Lerman, Carol B. Lindsley, Katherine L. Madson, Gulnara Mamyrova, Diana Milojevic, Stephen R. Mitchell, Renee Modica, Linda Myers, Kabita Nanda, Simona Nativ, Terrance O’Hanlon, Judyann C. Olson, Lauren M. Pachman, Murray H. Passo, Maria D. Perez, Donald A. Person, Marilyn G. Punaro, Linda I. Ray, Robert M. Rennebohm, Rafael F. Rivas-Chacon, Tova Ronis, Margalit Rosenkranz, Deborah Rothman, Adam Schiffenbauer, Bracha Shaham, Susan Shenoi, David Sherry, David Siegel, Abigail Smukler, Jennifer Soep, Matthew Stoll, Sangeeta H. Sule, Robert Sundel, Stacey Tarvin, Melissa Tesher, Scott A. Vogelgesang, Rita Volochayev, Dawn Wahezi, Jennifer C. Wargula, Peter Weiser, Pamela Weiss, Patience H. White, Andrew Zeft, Lawrence S. Zemel, Yongdong Zhao.