Lupus erythematosus (LE) and rheumatoid arthritis (RA) are groups of defects in microdebridement of tissue which includes removal of infectious agents and cellular debris. They are the phenotypic response to a number of polygenetic and/or induced defects. The recognized clinical patterns of these disorders are the responses to accumulated tissue debris and complications of secondary debridement mechanisms that cannot function properly due to basic defects in the debridement system.

The series of events that occurs after infection or tissue damage is polygenetic and involve multiple pathways. Genetic polymorphism of this group of mechanisms increases survival against a wider variety of infections. An organism capable of bypassing or destroying a specific step in the host defense is still eliminated by the host in spite of the created defect (a fault tolerant system). However, a single mutant error of this same step creating the same defect will not disrupt the host to the point of clinical illness or death. The pathways are broad enough to bypass some mutant errors. It is the same fault tolerant system. Increased pressure on the system from infection or tissue damage or a combination of multiple genetic defects results in enough faults to exceed the threshold of fault tolerance and produce clinical patterns of disease. The large number of possible combinations of defects gives rise to marked disease variation among patients. The higher frequency of some defects or combination of defects ces subsets.

Inbred strains of animals have less polymorphism and thus some strains have a greater susceptibility to infections, LE and RA.

Many of the phenomena that occur in LE and RA are secondary to the basic defect of inadequate tissue debridement. Rheumatoid factor (RF) is generally a normal beneficial phenomenon of increasing particle size so that immune complexes can more readily be removed by the reticuloendothelial system. In the presence of defective microdebridement the system is overloaded and no longer effective. This results in circulating RF.

There are clearly multiple basic genetic defects. For example, the known multiple genetic defects in complement in LE are relevant to the systems involved. They are important ligands for defense and debridement mechanisms. A null allele is not likely to be a secondary phenomenon. It might be in a fault tolerant site and contribute to disease in one host, and yet not contribute to disease in another host. A host with an overloaded microdebridement system is more susceptable to infections, including low grade pathogens.

Since a combination of defects may have to develop to present the clinical syndromes, lesser numbers (or less significant combinations) of defective genes would sometimes be present in relatives.

Autoantibodies are an example of a physiologic response to accumulated tissue debris. They occur when tissue damage is greater than can rapidly be removed or when there is inadequate tissue microdebridement. They are a universal biologic phenomenon for speeding tissue debridement in persons with normal debridement mechanisms. They produce problems in a person with defective microdebridement.