AUTOIMMUNE ENDOCRINE DISEASE

NIH GUIDE, Volume 22, Number 34, September 24, 1993



PA NUMBER:  PA-93-114



P.T. 34



Keywords:

  Autoimmunity 

  Endocrinology 

  Etiology 

  Pathogenesis 

  Disease Model 

  Biology, Molecular 



National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Allergy and Infectious Diseases



PURPOSE



The National Institute of Diabetes and Digestive and Kidney Diseases

(NIDDK) and the National Institute of Allergy and Infectious Diseases

(NIAID) invite investigator-initiated research grant applications

specifically targeted to study of the causes, etiology, pathogenesis,

and treatment of autoimmune endocrine diseases, and in particular

autoimmune thyroid disease and insulin-dependent diabetes mellitus.



HEALTHY PEOPLE 2000



The Public Health Service (PHS) is committed to achieving the health

promotion and disease prevention objectives of "Healthy People 2000,"

a PHS-led national activity for setting priority areas.  This program

announcement, Autoimmune Endocrine Disease, is related to the

priority area of research on women's health.  Potential applicants

may obtain a copy of Healthy People 2000 (Full Report:  Stock No.

017-001-00474-0) or Healthy People 2000 (Summary Report:  Stock No.

017-001-00473-1) through the Superintendent of Documents, Government

Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238).



ELIGIBILITY REQUIREMENTS



Applications may be submitted by domestic and foreign, for-profit and

non-profit organizations, public and private, such as universities,

colleges, hospitals, laboratories, units of State or local

governments, and eligible agencies of the Federal government.

Applications from minorities and women are encouraged.



MECHANISM OF SUPPORT



The mechanism of support for this program will be the research

project grant (R01).  The policies that govern the research grant

programs of the National Institutes of Health will prevail.  Support

for this solicitation is contingent upon receipt of appropriated

funds.  Since a variety of approaches would represent valid responses

to this solicitation, it is anticipated that there will be a range of

costs among individual grants awarded; however, it is anticipated

that awards will average approximately $200,000 per year in total

costs.  With respect to post-award administration, the current

policies and requirements that govern the research grant programs of

the NIH will prevail.



RESEARCH OBJECTIVES



The purpose of this initiative is to stimulate basic and clinical

research applications that will further the understanding of the

causes and therapeutic modalities of autoimmune endocrine diseases.



Background



Autoimmune endocrine diseases, including those involving the thyroid

(Graves' disease, Hashimoto's thyroiditis), insulin dependent

diabetes mellitus (IDDM), and Addison's disease are among the most

prevalent or common endocrine disorders.  These disorders often

strike young people, resulting in considerable loss of productivity

and long-term increases in health care costs.  Several of these

autoimmune endocrine diseases also have a higher incidence among

women, especially the autoimmune thyroid diseases, and in particular

Hashimoto's disease, the most common thyroid autoimmune disorder,

which has a four-fold greater incidence in women.  People with one

autoimmune endocrine disease are at increased risk for another of

these disorders, as are family members of patients with autoimmune

endocrine disease.  A recent NIDDK workshop entitled "Autoimmune

Thyroid Disease" brought together experts in autoimmune disease to

exchange state-of-the-art information in this field and identify

areas of scientific opportunity.  As a result of this workshop

several key research issues relevant to autoimmune endocrine diseases

were identified, including the underlying nature of autoimmunity, the

basis of increased incidence in women, and potential therapeutic

approaches to autoimmune diabetes and thyroid disease.



Recent observations have delineated many of the pathways that

regulate thyroid hormone release and metabolism. This, together with

improved assays for thyroid stimulating hormone (TSH), thyroid

autoantibodies, and an enhanced understanding of mechanisms of signal

transduction involving thyroid hormones has greatly improved the

laboratory and clinical assessment of thyroid function.

Nevertheless, for autoimmune endocrine diseases considerable

questions exist regarding the etiology, pathogenesis, and potential

treatments directed at the autoimmune basis of these diseases.  For

autoimmune thyroid diseases, several of the antigens that are

involved in the immune system responses, including the TSH receptor

for Graves' disease and thyroid peroxidase (TPO) for Hashimoto's

thyroiditis, have been identified.  For IDDM, several potential

antigens have been identified, including glutamic acid decarboxylase

(GAD).  In both instances, factors associated with autoimmune

diseases, including T-cell, B-cell, and HLA markers have been

implicated in disease initiation and progression.  Possible

therapeutic interventions have focused on immune system

interventions.  Nevertheless, the putative role(s) played by such

antigens in eliciting and/or contributing to autoimmune disease is

not known.  Clearly, a fuller understanding of the autoimmune basis

of these endocrine disorders is necessary to open the way for more

effective immune (and other) system approaches to disease treatment

and/or prevention.



Scope



Some examples of research topics that would be considered responsive

to this solicitation include, but are not limited to, the following:



o  the etiology, pathogenesis and treatment of autoimmune endocrine

diseases, including IDDM, autoimmune thyroid disease, and Addison's

disease

o  the cellular and molecular basis of autoimmune endocrine diseases

o  the molecular basis for the increased prevalence of autoimmune

endocrine diseases in women

o  the role of cytokines and growth factors in the etiology and/or

pathophysiology of autoimmune endocrine diseases

o  the mechanism of increased susceptibility to more than one

autoimmune endocrine disease

o  postpartum thyroiditis

o  experimental animal or tissue culture models for autoimmune

endocrine disorders

o  the role of islet cell antigens and antibodies and other potential

antigens in IDDM

o  extrathyroidal manifestations of autoimmune thyroid disease

o  potential therapeutic approaches to autoimmune endocrine diseases



These areas of interest are not listed in any order or priority.

They are only suggested examples of areas of research.  Applicants

are encouraged to propose other areas that are related to the

objectives and scope described above.



STUDY POPULATIONS



SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH

POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL

RESEARCH STUDY POPULATIONS



It is the NIH policy that women and minorities must be included in

clinical study populations unless there is a good reason to exclude

them, and the study design must seek to identify any pertinent gender

or minority population differences.  For foreign awards, the policy

on inclusion of women applies fully;  since the definition of

minority differs in other countries, the applicant must discuss the

relevance of research involving foreign  population groups to the

United States' populations, including minorities.



If the required information is not contained within the application,

the application will be returned.



Peer reviewers will address specifically whether the research plan in

the application conforms to these policies.  If the representation of

women or minorities in a study design is inadequate to answer the

scientific question(s) addressed AND the justification for the

selected study population is inadequate, it will be considered a

scientific weakness or deficiency in the study design and will be

reflected in assigning the priority score to the application.



All applications for clinical research submitted to NIH are required

to address these policies.  NIH funding components will not award

grants or cooperative agreements that do not comply with these

policies.



APPLICATION PROCEDURES



Applications are to be submitted on form PHS 398 (rev. 9/91), which

is available from an applicant institution's office of sponsored

research and the Office of Grants Information, Division of Research

Grants, National Institutes of Health, Westwood Building, Room 240,

Bethesda, MD 20892, telephone 301/710-0267.  Use the conventional

format for research project grant applications and ensure that the

points identified in this program announcement in the section REVIEW

PROCEDURES AND CRITERIA are fulfilled.  To identify the application

as a response to this Program Announcement, check "YES" on item 2a of

page one of the application and enter the title "Autoimmune Endocrine

Disease" and the program announcement number:  PA-93-114.



Applications will be accepted in accordance with the announced

receipt dates for new applications (see receipt dates and review

schedule in application kits).



The original and five copies of the application must be sent or

delivered to:



Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**



REVIEW CONSIDERATIONS



Applications will be received by the NIH, Division of Research Grants

(DRG), referred to an appropriate Initial Review Group (IRG) for

scientific merit review, and assigned to individual Institutes for

possible funding.  Referral decisions will be governed by normal

programmatic considerations as specified in the Referral Guidelines

of the PHS.  Some applications may receive dual assignment.

Applications will first be reviewed for scientific and technical

merit by an IRG composed primarily of non-federal scientific

consultants.  Following scientific-technical review, the applications

will receive a second-level review by the Institute's national

advisory council.



AWARD CRITERIA



Applications will compete for available funds with all other approved

applications assigned to NIDDK or NIAID. The factors to be considered

in making funding decisions include:



o  Quality of the proposed project as determined by peer review

o  Availability of funds

o  Program balance among research areas of the announcement



INQUIRIES



Written and telephone inquiries are encouraged.  The opportunity to

clarify any issues or questions from potential applicants is welcome.



Direct inquiries regarding programmatic issues to:



Ronald N. Margolis, Ph.D.

Division of Diabetes, Endocrinology and Metabolic Diseases

National Institute of Diabetes and Digestive and Kidney Diseases

Westwood Building, Room 621

Bethesda, MD  20892

Telephone:  (301) 594-7549

FAX:  (301) 594-9011



Elaine Collier, M.D.

Division of Allergy, Immunology, and Transplantation

National Institute of Allergy and Infectious Diseases/NIH

Solar Building, Room 4A-20

Bethesda, MD  20892

Telephone:  (301) 496-7985

FAX:  (301) 402-2571



Direct inquiries regarding fiscal matters to:



Ms. Kim Law

Grants Management Branch

National Institute of Diabetes and Digestive and Kidney Diseases

Westwood Building, Room 549D

Bethesda, MD  20892

Telephone:  (301) 594-7543



AUTHORITY AND REGULATIONS



This program is described in the Catalog of Federal Domestic

Assistance Nos. 93.847 and 93.855.  Awards are made under

authorization of the Public Health Service Act, Title IV, Part A

(Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and

285) and administered under PHS grants policies and Federal

Regulations 42 CFR 52 and 45 CFR Part 74.  This program is not

subject to the intergovernmental review requirements of Executive

Order 12372 or Health Systems Agency review.



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